Shigella spp.

I. Organism Information

A. Taxonomy Information
  1. Species:
    1. Shigella boydii :
      1. Ontology: UMLS:C0036955
      2. GenBank Taxonomy No.: 621
      3. Description: Shigella is a group of Gram-negative, facultative intracellular pathogens. Recognized as the etiologic agents of bacillary dysentery or shigellosis in the 1890s, Shigella was adopted as a genus in the 1950s and subgrouped into four species: Shigella dysenteriae, Shigella flexneri, Shigella boydii and Shigella sonnei (also designated as serogroups A to D) (Yang et al., 2005). There are very few biochemical properties that can distinguish Shigella from enteroinvasive Escherichia coli (EIEC), which are also a major cause of dysentery. Indeed, some O-antigens associated with EIEC are identical to those found in Shigella spp., and many plasmid-associated virulence determinants are common to both EIEC and Shigella (Yang et al., 2005). Escherichia coli and Shigella species have been historically treated as different species, but recent studies indicate that Shigella strains are in reality clones of E. coli, based on comparison of their housekeeping genes (Tao et al., 2005). Shigella boydii. This species is uncommon except in India, where it was first isolated. The 18 known serotypes are antigenically distinct, expressing a diverse range of toxins in addition to a Shigella-specific toxin. Progression to clinical dysentery occurs in most patients infected with this organism (NCBI Entrez Genome Project).
      4. Variant(s):
        • Shigella boydii BS512 :
          • GenBank Taxonomy No.: 344609
          • Parent: Shigella boydii
          • Description: This strain (strain BS512; serotype 18) was originally isolated from a 12-year-old boy in Arizona by Dr. Nancy Stockbine. It is a member of Group 1 as determined by limited sequence analysis and can invade HeLa cells. Pathogenicity and virulence have been verified during in vitro experimentation, and multiple plasmids are present in this strain (NCBI Entrez Genome Project).
    2. Shigella dysenteriae :
      1. Ontology: UMLS:C0036956
      2. GenBank Taxonomy No.: 622
      3. Description: Since the late 1960s, pandemic waves of Shiga (S. dysenteriae type 1) dysentery have appeared in Central America, south and south-east Asia and sub-Saharan Africa, often affecting populations in areas of political upheaval and natural disaster. When pandemic S. dysenteriae type 1 strains invade these vulnerable populations, the attack rates are high and dysentery often becomes a leading cause of death (Kotloff et al., 1999). Synonyms: Shigella shigae, Eberthella dysenteriae, Bacillus shigae, Bacillus dysenteriae, Bacillus dysentericus (NCBI Taxonomy).
      4. Variant(s):
        • Shigella dysenteriae 1012 :
          • GenBank Taxonomy No.: 358708
          • Parent: Shigella dysenteriae
          • Description: This serotype 4 strain was isolated in Bangledesh and provided by Maj. Carl Brinkley (Walter Reed Army Institute of Research). This strain is representative of the type 4 group of S. dysenteriae that is becoming more prevalent in human infections. This shift is towards the type 2 and type 4 serotypes, which were not previously associated with outbreaks, and away from the type 1 serotype, which was implicated in widespread epidemics in Asia, Central America, and Africa. Pathogenicity has been confirmed in human challenge experiments and strain 1012 has been shown to be one of the most virulent S. dysenteriae strains identified by WRAIR/NMRC to date. This strain contains multiple plasmids thought to be involved in virulence (NCBI Entrez Genome Project).
    3. Shigella flexneri :
      1. Ontology: UMLS:C0036957
      2. GenBank Taxonomy No.: 623
      3. Description: S. flexneri is endemic in most developing countries and causes more mortality than any other Shigella species. The predominant serotypes of S. flexneri in developing countries are serotypes 1b, 2a, 3a, 4a and 6, whilst in industrialized countries most isolates are 2a (Jennison and Verna, 2004). Synonym: Shigella paradysenteriae (NCBI Taxonomy)
      4. Variant(s):
        • Shigella flexneri 2a :
          • GenBank Taxonomy No.: 42897
          • Parent: Shigella flexneri
          • Description: In developing countries, the predominant serotype of S. flexneri is 2a, followed by 1b, 3a, 4a, and 6. In industrialized countries, most isolates are S. flexneri 2a or other unspecified type 2 strains (Kotloff et al., 1999). Shigella flexneri 2a str. 2457T. This is a highly virulent strain that has been widely used for genetic and clinical research. It is similar to pathogenic Escherichia coli except for the more numerous insertion sequences and contains 4 plasmids pINV-2457T, pSf2, and pSf4, and pSf-R27 that are similar to pWR100, pWR501, pCP301, and R27 respectively (NCBI Entrez Genome Project). Shigella flexneri 2a str. 301. This strain was isolated in 1984 from a patient in Beijing, China. It is similar to pathogenic Escherichia coli except for the more numerous insertion sequences and contains a virulence plasmid (pCP301) (NCBI Entrez Genome Project). Synonym: Shigella flexneri serotype 2a (NCBI Taxonomy).
        • Shigella flexneri 2a str. 2457T :
          • GenBank Taxonomy No.: 198215
          • Parent: Shigella flexneri 2a
          • Description: Shigella flexneri 2a str. 2457T. This is a highly virulent strain that has been widely used for genetic and clinical research. It is similar to pathogenic Escherichia coli except for the more numerous insertion sequences and contains 4 plasmids pINV-2457T, pSf2, and pSf4, and pSf-R27 that are similar to pWR100, pWR501, pCP301, and R27 respectively (NCBI Entrez Genome Project).
        • Shigella flexneri 2a str. 301 :
          • GenBank Taxonomy No.: 198214
          • Parent: Shigella flexneri 2a
          • Description: This strain was isolated in 1984 from a patient in Beijing, China. It is similar to pathogenic Escherichia coli except for the more numerous insertion sequences and contains a virulence plasmid (pCP301) (NCBI Entrez Genome Project).
        • Shigella flexneri 5 :
          • GenBank Taxonomy No.: 373383
          • Parent: Shigella flexneri
          • Description: This organism, along with Shigella sonnei, is the major cause of shigellosis in industrialized countries and is responsible for endemic infections (NCBI Genome Project).
    4. Shigella sonnei :
      1. Ontology: UMLS:C0036960
      2. GenBank Taxonomy No.: 624
      3. Description: Synonym: Bacterium sonnei (NCBI Taxonomy). Shigella dysenteriae and Shigella sonnei are the predominant species in the tropics, while S. sonnei is the predominant species in industrialized countries (Alcoba-Florez et al., 2005).
      4. Variant(s):
B. Lifecycle Information :
  1. Shigella spp. :
    1. Shape: Rod (NCBI Genome Project)
    2. Picture(s):
      1. SEM Image of Shigella dysenteriae (Website 53):



        Description: Shigella dysenteriae - rod prokaryote (bacterium) Dennis Kunkel Microscopy Inc (Website 53).
      2. SEM Image of Shigella sonnei (Website 53):



        Description: Shigella sonnei - rod prokaryote (bacterium). Dennis Kunkel Microscopy Inc (Website 53).
    3. Description: Organisms of the genus Shigella belong to the tribe Escherichia in the family Enterobacteriaceae. It is a small, uncapsulated, nonsporulating facultative anaerobic bacilli (Niyogi, 2005).

  2. Description: The bacteria are primarily transmitted through the faecal-oral route (Yang et al., 2005).
C. Genome Summary:
  1. Genome of Shigella boydii
    1. Chromosome (NCBI Entrez Genome):
      1. GenBank Accession Number: NC_007613
      2. Size: 4,519,823 (NCBI Entrez Genome)
      3. Gene Count: 4466 Genes. 4136 Proteins (NCBI Entrez Genome).
      4. Description:
    2. Plasmid pSB4_227 (NCBI Entrez Genome):
      1. GenBank Accession Number: NC_007608
      2. Size: 126,697 (NCBI Entrez Genome)
      3. Gene Count: 149 Genes. 148 Proteins (NCBI Entrez Genome).
      4. Description:

  2. Genome of Shigella boydii BS512
    1. Description: The Shigella boydii BS512 whole genome shotgun (WGS) project has the project accession NZ_AAKA00000000. This version of the project (01) has the accession number NZ_AAKA01000000, and consists of sequences NZ_AAKA01000001-NZ_AAKA01000079 (NCBI Entrez Genome).
    2. Chromosome (NCBI Entrez Genome):
      1. GenBank Accession Number: NZ_AAKA00000000
      2. Size: 4680 Genes. 4680 Proteins (NCBI Entrez Genome).
      3. Gene Count: 4,900,244 (NCBI Entrez Genome)
      4. Description:

  3. Genome of Shigella dysenteriae Sd197
    1. Chromosome (NCBI Entrez Genome):
      1. GenBank Accession Number: NC_007606
      2. Size: 4,369,232 (NCBI Entrez Genome)
      3. Gene Count: 4664 Genes. 4274 Proteins (NCBI Entrez Genome).
      4. Description:
    2. Plasmid pSD1_197 (NCBI Entrez Genome):
      1. GenBank Accession Number: NC_0076076
      2. Size: 182,726 (NCBI Entrez Genome)
      3. Gene Count: 224 Genes. 223 Proteins (NCBI Entrez Genome).
      4. Description:

  4. Genome of Shigella dysenteriae 1012
    1. Chromosome (NCBI Entrez Genome):
      1. GenBank Accession Number: NZ_AAMJ00000000
      2. Size: 3,013,140 (NCBI Entrez Genome)
      3. Gene Count: 2782 Genes. 2782 Proteins (NCBI Entrez Genome).
      4. Description:

  5. Genome of Shigella flexneri 2a str. 2457T
    1. Description: We determined the complete genome sequence of Shigella flexneri serotype 2a strain 2457 (Wei et al., 2003). The genome exhibits the backbone and island mosaic structure of E. coli pathogens, albeit with much less horizontally transferred DNA and lacking 357 genes present in E. coli. The strain is distinctive in its large complement of insertion sequences, with several genomic rearrangements mediated by insertion sequences, 12 cryptic prophages, 372 pseudogenes, and 195 S. flexneri-specific genes. The 2457T genome was also compared with that of a recently sequenced S. flexneri 2a strain, 301. Our data are consistent with Shigella being phylogenetically indistinguishable from E. coli (Wei et al., 2003).
    2. Chromosome (NCBI Entrez Genome):
      1. GenBank Accession Number: NC_004741
      2. Size: 4,599,354 (NCBI Entrez Genome)
      3. Gene Count: 4577 Genes. 4068 Proteins (NCBI Entrez Genome).
      4. Description: The genome consists of a single circular chromosome of 4,599,354 bp with a G+C content of 50.9% (Wei et al., 2003). Base pair 1 of the chromosome was assigned to correspond with bp 1 in E. coli K-12, since the two strains share extensive homology. The origin and terminus of replication were identified within homologous regions. The genome encodes 4,084 predicted genes, with an average size of 873 bp (926 bp if insertion sequences are excluded). The genome is slightly smaller than that of K-12 (4,639,221 bp), and its organization is roughly similar to that described for pathogenic E. coli strain O157:H7 EDL933 and the uropathogen CFT073, with large regions of colinear E. coli backbone punctuated by islands of sequence presumably acquired by horizontal transfer. The number of islands is smaller than those in CFT073 and O157:H7, and a larger proportion of the genome is backbone (82% versus 75% for O157:H7 and CFT073). There are 15 rearrangements greater than 5kb in the genome (inversions and translocations) detected by comparison with K-12. Seven rRNA operons are present; their organization was altered from that in K-12 by genomic rearrangements. Ninety-eight tRNA genes include three copies of a novel cluster of four tRNAs (Ile, Arg, Thr, and Gly); only one of these (Gly) is identical to a K-12 tRNA. Each cluster in 2457T is in a prophage region, positioned downstream of the phage Q gene, as in the EDL933 Stx2 phage 933W (Wei et al., 2003)

  6. Genome of Shigella flexneri 2a str. 301
    1. Description: The whole genome is composed of a 4,607,203 bp chromosome and a 221,618 bp virulence plasmid, designated pCP301 (Jin et al., 2002).
    2. Chromosome (NCBI Entrez Genome):
      1. GenBank Accession Number: NC_004337
      2. Size: 4,607,203 (NCBI Entrez Genome)
      3. Gene Count: 4566 Genes. 4182 Proteins (NCBI Entrez Genome).
      4. Description: While the plasmid shows minor divergence from that sequenced in serotype 5a, striking characteristics of the chromosome have been revealed. The S. flexneri chromosome has, astonishingly, 314 IS elements, more than 7-fold over those possessed by its close relatives, the non-pathogenic K12 strain and enterohemorrhagic O157:H7 strain of Escherichia coli. There are 13 translocations and inversions compared with the E. coli sequences, all involve a segment larger than 5 kb, and most are associated with deletions or acquired DNA sequences, of which several are likely to be bacteriophage-transmitted pathogenicity islands. Furthermore, S. flexneri, resembling another human-restricted enteric pathogen, Salmonella typhi, also has hundreds of pseudogenes compared with the E. coli strains (Jin et al., 2002).
    3. Plasmid pCP301 (NCBI Entrez Genome):
      1. GenBank Accession Number: NC_004851
      2. Size: 221,618 (NCBI Entrez Genome)
      3. Gene Count: 267 Genes. 261 Proteins (NCBI Entrez Genome).
      4. Description: Like previously sequenced virulence plasmids (pWR100 and pWR501) from serotype 5a strains, pCP301 is a mosaic of potential virulence-related genes, IS elements, maintenance genes and functionally unknown ORFs. All the previously identified virulence genes are present in pCP301. These include the primary invasion genes ipa and mxi-spa (encoding the invasion plasmid antigens and the type III secretion system, respectively), virG/IcsA (required for polymerizing host actin to provide propelling force for intra- and inter-cellular spread) and virF (necessary for regulating virulence gene expression). The replication origin (R100-like) ori and G site (single-strand initiation site) in pCP301 are identical to those of pWR501 and pWR100. pCP301 also has maintenance genes, repA, copA and copB, for replication; parA and parB for partitioning; and ccdA and ccdB for post-segregation killing. The noticeable difference between pCP301 and the plasmids from serotype 5a is the presence of more IS-related DNA in pCP301, making its size close to pWR501 (221 851 bp) which is larger than pWR100 because of a Tn501 (8360 bp) insertion. So, both Shigella serotypes most likely acquired the ancestral virulence plasmid from the same source. One other minor divergence is that the ipa-mxi-spa loci in pWR501 and pCP301 are in the same orientation, whereas in pMYSH6000, the virulence plasmid from another 2a strain, they are in inverse orders. This indicates that the divergence of the plasmids does not necessarily correlate with serotypes (Jin et al., 2002).

  7. Genome of Shigella flexneri 2a
    1. Plasmid p2457TS2 (NCBI Entrez Genome):
      1. GenBank Accession Number: NC_002773
      2. Size: 3,179 (NCBI Entrez Genome)
      3. Description: Submitted (03-MAR-2001). Wang,H., Feng,E., Liao,X., Su,G. and Huang,C.. Unpublished (NCBI Entrez Genome).

  8. Genome of Shigella flexneri 5
    1. Plasmid pWR501 (NCBI Entrez Genome):
      1. GenBank Accession Number: NC_002698
      2. Size: 221,851 (NCBI Entrez Genome)
      3. Gene Count: 293 Genes. 293 Proteins (NCBI Entrez Genome).
      4. Description: S. flexneri wild-type serotype 5a strain M90T, harboring pWR100, was crossed with E. coli MC1061 carrying pMT999, a Tn501-labeled, self-transmissible, temperature-sensitive plasmid. The cross resulted in M90T carrying a cointegrate of pWR100 and pMT999, which was subsequently mobilized into E. coli 395-1 by conjugation. Following passage of this strain at 42 C with appropriate antibiotic selection, a pWR100 derivative from which pMT999 had been lost and in which the Tn501 integration was retained was isolated and designated pWR501. This E. coli strain, which lacks the two smaller Shigella plasmids, was the source for the isolation of virulence plasmid DNA (Venkatesan et al., 2002). Most of the known Shigella virulence determinants are encoded on a large plasmid that is unique to virulent strains of Shigella and enteroinvasive Escherichia coli; these known genes account for approximately 30 to 35% of the virulence plasmid. In the complete sequence of the virulence plasmid, 286 open reading frames (ORFs) were identified. An astonishing 153 (53%) of these were related to known and putative insertion sequence (IS) elements; no known bacterial plasmid has previously been described with such a high proportion of IS elements. Four new IS elements were identified. Fifty putative proteins show no significant homology to proteins of known function; of these, 18 have a G+C content of less than 40%, typical of known virulence genes on the plasmid. These 18 constitute potentially unknown virulence genes. Two alleles of shet2 and five alleles of ipaH were also identified on the plasmid. Thus, the plasmid sequence suggests a remarkable history of IS-mediated acquisition of DNA across bacterial species (Venkatesan et al., 2002).

  9. Genome of Shigella sonnei Ss046
    1. Chromosome (NCBI Entrez Genome):
      1. GenBank Accession Number: NC_007384
      2. Size: 4,825,265 (NCBI Entrez Genome)
      3. Gene Count: 4553 Genes. 4223 Proteins (NCBI Entrez Genome).
      4. Description:
    2. Plasmid pSS (NCBI Entrez Genome):
      1. GenBank Accession Number: NC_007385
      2. Size: 214,396 (NCBI Entrez Genome)
      3. Gene Count: 241 Genes. 248 Proteins (NCBI Entrez Genome).
      4. Description: The complete sequence of pSS, which is the large virulence plasmid of Shigella sonnei, was determined. The 214-kb plasmid is composed of segments of virulence-associated genes, the O-antigen gene clusters, a range of replication and maintenance genes, and large numbers of insertion sequence (IS) elements. Two hundred and forty-one open reading frames (ORFs) were identified, of which 117 are highly homologous to IS elements or transposases, 57 are homologous to known pathogenesis-associated proteins, and 30 are related to replication, plasmid maintenance, or other metabolic functions. Thirty-seven ORFs have no similarity to proteins with a known function, including two with no significant similarity to any hypothetical proteins. Interestingly, 10 ORFs encoding O-antigen gene clusters were identified on the plasmid and this is markedly different from most other Shigella spp. virulent plasmids. A novel toxin-antitoxin system, a series of stbDE homologs, was found on the plasmid immediately downstream of the replication region; the sole segregation stability system may be responsible for the instability of pSS. The pSS plasmid is a mixture of genes with different origins and functions. The sequence suggests a remarkable history of IS-mediated recombination and acquisition of DNA across a range of bacterial species (Jiang et al., 2005). Similar to the other three groups of Shigella, the virulence plasmid of S. sonnei, designated as pSS, is sufficient for entering, replicating, and disseminating within epithelial cells. However, pSS is unstable and tends to be lost at a high frequency, unlike other large unicopy plasmids. In addition, experiments have shown that an O-antigen gene cluster, commonly found in the chromosomes of Shigella spp., is actually contained on this plasmid (Jiang et al., 2005)

  10. Genome of Shigella sonnei
    1. Description: Colicins are plasmid-encoded toxic exoproteins that are produced by colicinogenic strains of Escherichia coli and some related species of the family Enterobacteriaceae. To date, at least 23 colicin types have been described in detail (Smajs and Weinstock, 2001). Colicin Js was originally described as a bacteriocin of Shigella sonnei colicinotype 7. In 1987, colicin type 7 was reclassified in accordance with Fredericq's original classification scheme and designated colicin Js. Its particular physicochemical and biological characteristics were published. For a number of reasons, colicin Js appeared to be a rather exceptional colicin type: producer bacteria, as well as the indicator strain S. sonnei 17 (colicin type 6), were involved in outbreaks of epidemic diarrhea. Colicin Js showed a unique antimicrobial spectrum, being inactive against standard E. coli colicin indicators. Indirect fluorimetry measurements indicated that the mode of action of colicin Js was not analogous to that of either pore-forming or nuclease-type colicins. Colicin Js was shown to be active against enteroinvasive E. coli (EIEC) serotypes. The sensitivity to Js was 90% associated with the ability of EIEC strains to produce experimental keratoconjunctivitis in rabbits. Strains belonging to EIEC serotypes that were not sensitive to colicin Js were, as a rule, negative in the enteroinvasiveness test (Smajs and Weinstock, 2001).
    2. Plasmid ColJs (NCBI Entrez Genome):
      1. GenBank Accession Number: NC_002809
      2. Size: 5,210 (NCBI Entrez Genome)
      3. Gene Count: 3 Genes. 3 Proteins (NCBI Entrez Genome).
      4. Description: The 5.2-kb ColJs plasmid of a colicinogenic strain of Shigella sonnei (colicin type 7) was isolated and sequenced. pColJs was partly homologous to pColE1 and to pesticin-encoding plasmid pPCP1, mainly in the rep, mob, and cer regions. A 1.2-kb unique region of pColJs showed significantly different G+C content (34%) compared to the rest of pColJs (53%). Within the unique region, seven open reading frames (ORFs) were identified. ORF94 was shown to code for colicin Js activity (cja), a 94-amino-acid polypeptide (molecular mass, 10.4 kDa); ORF129 (cji) was shown to code for the 129-amino-acid colicin Js immunity protein (molecular mass, 14.3 kDa); and ORF65 was shown to be involved in colicin Js release by producer bacteria (cjl) coding for a 65-amino-acid polypeptide (molecular mass, 7.5 kDa) (Smajs and Weinstock, 2001).

II. Epidemiology Information

The annual number of Shigella episodes worldwide is estimated to be 165 million, of which more than 100 million occur in the developing world with more than 1 million deaths (Dupont, 2005). Although Shigella is endemic worldwide, it affects certain populations more than others. In developing countries, high rates of morbidity and mortality are known to occur among displaced populations. Using the USA as an example, identified risk groups in industrialized countries include children in day-care centres, native Americans on reservations, patients in custodial institutions, and homosexual men, which together account for approximately 13% of reported isolates; international travelers and their household contacts are responsible for an additional 20% (Kotloff et al., 1999) The majority (median 60%, range 25-86%) of Shigella isolates from developing countries are S. flexneri, with S. sonnei being the next most common (median 15%, range 2-44%). S. dysenteriae (median 6%, range 1-31%) and S. boydii (median 6%, range 0-46%) occur equally frequently. S. dysenteriae is seen most often in South Asia and sub-Saharan Africa. In contrast, data from Israel, Spain, and the USA consistently demonstrate that S. sonnei is the most common serogroup found in industrialized countries (median 77%, range 74-89%), followed by S. flexneri (median 16%, range 10-21%), S. boydii (median 2%, range 2-5%) and finally S. dysenteriae (median 1%, range 0-1%) (Kotloff et al., 1999).

A. Outbreak Locations:
  1. During 1967-70, bacillary dysentery was first reported in Central American countries. Since then, spread of this infection has been reported from many Asian countries such as Bangladesh (1972-78, 2003), Sri Lanka (1976), Maldives (1982), Nepal (1984-85), Bhutan (1984-85) and Myanmar (1984-85). In India, epidemics were mainly encountered in southern India (Vellore - 1972-73, 1997-2001), eastern India (1984) and Andaman and Nicobar islands (1986). Recent outbreaks (2002-03) of multi drug resistant S. dysenteriae type 1 have been reported from Siliguri, Diamond Harbour, Kolkata, and Aizwal and Bangladesh (Sur et al., 2004).
  2. Shigella dysenteriae. Since the late 1960s, pandemic waves of Shiga (S. dysenteriae type 1) dysentery have appeared in Central America, south and south-east Asia and sub-Saharan Africa, often affecting populations in areas of political upheaval and natural disaster. When pandemic S. dysenteriae type 1 strains invade these vulnerable populations, the attack rates are high and dysentery often becomes a leading cause of death (Kotloff et al., 1999).
  3. Africa-Shigella dysenteriae. In November 1999, a Medecins Sans Frontieres team based in the southeastern part of Sierra Leone reported an increased number of cases of bloody diarrhoea. Shigella dysenteriae serotype 1 (Sd1) was isolated in the early cases. A total of 4,218 cases of dysentery were reported in Kenema district from December, 1999, to March, 2000. The overall attack rate was 7.5%. The attack rate was higher among children younger than 5 years than in the rest of the population (11.2% vs 6.8%; relative risk=1.6; 95% CI 1.5-1.8). The case fatality was 3.1%, also higher for children younger than 5 years (6.1% vs 2.1%; relative risk=2.9; 95% CI 2.1-4.1]). Among 583 patients regarded at increased risk of death who were treated with ciprofloxacin in isolation centres, case fatality was 0.9%. A 5-day ciprofloxacin regimen, targeted to the most severe cases of bloody diarrhoea, was highly effective. This is the first time a large outbreak caused by Sd1 has been reported in west Africa (Guerin et al., 2003).
  4. New York, USA-Shigella flexneri. On 31 May 2001, the Nassau County Department of Health (NCDH) in New York state notified the CDC of a large outbreak of gastrointestinal illness involving 5 local restaurants (hereafter referred to as restaurants A-E) under the same ownership. They reported culture-confirmed S. flexneri infection in 4 persons, all of whom had eaten at restaurant A before onset of illness. Subsequently, a nurse reported diarrhea in 19 of 70 persons who ate a hospital lunch catered by restaurant A on 24 May. Reports of illness in persons who had eaten at 4 other local restaurants (restaurants B-E) followed. The NCDH inspected the restaurants, obtained samples of prepared food, and destroyed the remaining food on 30 May. Workers were asked about illness and were required to submit a stool sample for culture. S. flexneri was isolated from the feces of 2 ill and 14 asymptomatic employees, and they were excluded from work. On 2 June, a team from the CDC arrived to evaluate the extent of the outbreak, identify the vehicle and source of contamination, and implement prevention and control measures (Reller et al., 2006). More than 1,500 persons called the NCDH during the outbreak to report 886 illnesses. The NCDH received reports of 117 fecal cultures that grew S. flexneri; 116 were associated with the outbreak (Reller et al., 2006). This is the largest documented foodborne outbreak of S. flexneri infection, and the first epidemiologically linked to tomatoes. We believe that tomatoes, contaminated most likely at a terminal distribution site, started the outbreak that involved 5 restaurants under a single owner. Consumption of tomatoes was the only exposure that remained significant in multiple multivariable models. Within 24 h after the arrival of hand-sorted, bruised "special grade" tomatoes from a new distributor, the rate of illness peaked at each restaurant. No other establishment received "special grade" tomatoes, and heightened surveillance did not detect the outbreak strain of S. flexneri 2a elsewhere, locally or nationally. These findings suggest that tomatoes contaminated at a final distribution site, rather than at a more central site of production, processing, or distribution, caused the outbreak (Reller et al., 2006).
  5. Spain-Shigella sonnei. A large outbreak of Shigella sonnei gastroenteritis occurred in Murcia Region (Southeast Spain) in the winter of 1995-1996. More than 200 people were affected. Epidemiological investigations implicated a regionally manufactured fresh pasteurised milk cheese as the vehicle of infection. A case-control study showed a statistically significant association between the illness and consumption of the suspect cheese. The dispersed sale of the cheese resulted in a regional dissemination of the organism and people were affected in eight townships. Research suggested that an infected foodhandler at the cheese factory might have been the source of contamination and that the processing method might have allowed cross-contamination to occur (Garcia-Fulgueiras et al., 2001).
  6. Bangladesh-Shigella dysenteriae. From January 1999 to December 2002, a total of 358 S. dysenteriae strains isolated from patients attending the Dhaka treatment centre operated by the International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR, B), Centre for Health and Population Research, were initially identified in the Clinical Microbiology Laboratory by standard microbiological and biochemical methods (Talukder et al., 2005). From 8 June 2000, the number of S. dysenteriae type 4 increased dramatically and a total of 71 strains were isolated by December 2000, as compared to 1, 24 and 6 isolates in 1999 (pre-outbreak), 2001 and 2002 (post-outbreak), respectively. Thus the number of cases of shigellosis caused by S. dysenteriae type 4 peaked during the period from June to December 2000, suggesting the clustering of a single serotype of S. dysenteriae strains. During this period, 59 % of cases of infection occurred in children less than 5 years old and the infection rate was higher in males (61 %) as compared to females (39 %). This age and sex distribution is similar to that of the patients treated at the ICDDR, B hospital. All of the 102 strains of S. dysenteriae 4 were resistant to sulfamethoxazole-trimethoprim, and 12.3 % (n = 13) and 4.2 % (n = 4) of strains were resistant to ampicillin and nalidixic acid, respectively, while all the strains were sensitive to ciprofloxacin and mecillinam (Talukder et al., 2005).
B. Transmission Information:
  1. From: Human To: Human , With Destination: Human
    Mechanism: Mechanical Transmission. Flies may be important in the transmission of bacillary dysentery, especially in tropical climates. Dysentery in warm countries is most prevalent when the fly population is at its highest. Bacteriologic surveys of fly populations indicate that flies can occasionally be shown to be positive for Shigella bacteria. The low dose required for infection at least partially explains the potential for fly-transmission of shigellosis (Dupont, 2005).

  2. From: Human To: Human , With Destination: Human
    Mechanism: Fecal/Oral Transmission. Most transmission is by person-to-person spread, but infection is also caused by ingestion of contaminated food or water. Shigellosis is most common in situations in which hygiene is limited (e.g., child care centers and other institutional setting). In populations without running water and indoor plumbing, shigellosis can become an endemic problem. Sexual transmission of Shigella among men who have sex with men also occurs (Bopp et al., 2003).

  3. From: Primate To: Human , With Destination: Human
    Mechanism: Zoonotic Transmission. A small cluster of dysenteric illness, due to Shigella flexneri, was identified among technical assistants of a primate research unit. All of the affected individuals had been in regular contact with a colony of cynomolgus macaque monkeys, one of which was known to have suffered from acute haemorrhagic colitis in the preceding few weeks. Four monkeys were found to be excreting S. flexneri bacilli of identical antigen type (1b) to that isolated from the human cases. Investigation of working practices revealed the potential for inadvertent faeco-oral spread and the need to improve existing control methods. We conclude that this small outbreak of shigellosis represents a primate-associated occupational zoonosis (Kennedy et al., 1993). During two dysentery outbreaks in primate pet owners, Shigella and Salmonella strains were isolated from the enteric flora. In both outbreaks the source of infection was traced to asymptomatic spider monkeys (Ateles geoffroyi) (Fox, 1975). A fatal case of human shigellosis was associated with an asymptomatic spider monkey shedding Sh. flexneri 2a. This pathogen was isolated from the patient's stool and from the colon of the monkey at necropsy (Fox, 1975).

C. Environmental Reservoir:
  1. Humans :
    1. Ontology: UMLS:C0020114
    2. Description: Shigellosis is a highly contagious disease caused by Shigella spp. and humans are the principal reservoir of infection (Sur et al., 2004).
    3. Survival Information: Shigella remain viable for a limited time outside the human body (Niyogi, 2005). S. dysenteriae type 1 was inoculated onto cloth, wood, plastic, aluminum, and glass objects. Results showed that 1.5-4.0 hours after inoculation, S. dysenteriae type 1 became non-culturable, and after five days, non-culturable but viable S. dysenteriae type 1 could be detected by both PCR and fluorescent antibody techniques (Islam et al., 2001).
D. Intentional Releases:
  1. Intentional Release information :
    1. Description: In 1997, a laboratory worker intentionally contaminated his co-workers' food with a strain of Shigella stolen from the laboratory. While the Shigella strain did cause severe gastroenteritis and several hospitalizations, the use of this strain deviates from the popular idea of a bioterrorist's preferred weapon (Ashford et al., 2003).
    2. Emergency contact: Shigellosis is a reportable disease. Physicians suspecting this diagnosis should contact their local public health unit to initiate investigations into its source (Weir, 2002).

III. Infected Hosts

  1. Homo sapiens:
    1. Taxonomy Information:
      1. Species:
        1. Human :
          • Ontology: UMLS:C0086418
          • GenBank Taxonomy No.: 9606
          • Scientific Name: Homo sapiens (NCBI Taxonomy)
          • Description: Acute diarrhoeal diseases rank second amongst all deaths due to infectious diseases accounting for 3.1 million deaths in under 5 children; 80 per cent of these deaths occur in children below 2 yr of age. Shigellosis is an important cause of diarrhoeal deaths. It has been reported that no less than 140 million cases of shigellosis occur worldwide with 600,000 deaths annually; 60 per cent of such deaths are seen in under 5 children (Sur et al., 2004).

    2. Infection Process:
      1. Infectious Dose: Bacillary dysentery is one of the most, if not the most, communicable of the bacterial diarrheas. Experiments in volunteers have demonstrated that shigellosis is unique among bacterial enteropathogens in that fewer than 200 viable cells can readily produce the disease in healthy volunteers (Dupont, 2005). Under experimental conditions, ingestion of as few as 10 organisms can cause disease in 10% of North American volunteers, and ingestion of 500 organisms routinely causes disease in 50% of these volunteers. The reason(s) for the low 50% infective dose of Shigella species is not readily apparent, but the relative resistance of shigellae to stomach acid when compared with salmonellae or E. coli may facilitate the survival of small numbers of ingested organisms and provide the opportunity for organisms to infect the intestinal mucosa (Hale, 1991).
      2. Description: Shigella species invade the colonic and rectal epithelium of primates and humans, causing the acute mucosal inflammation characteristic of shigellosis. Infection is usually confined to the superficial layer of the colonic mucosa, where severe tissue damage leads to abscesses and ulceration. Destruction of the epithelial layer leads to the clinical symptoms of watery diarrhoea, severe abdominal pain and cramping, eventuating in the bloody mucoid stool characteristic of bacillary dysentery (Jennison and Verna, 2004)

    3. Disease Information:
      1. Acute Bacterial Dysentery (i.e., Shigellosis) :
        1. Pathogenesis Mechanism: The current model on mechanisms of pathogenesis induced by bacteria belonging to Shigella spp. are derived from in vitro and in vivo studies using various cell types (epithelial cells, macrophages, monocytes, fibroblasts and red blood cells) and animal models of infection, such as the cornea in guinea pigs, ligated ileal loops in rabbits and lungs in mice, in which bacteria induce an inflammatory response leading to destruction of the corresponding epithelium. In the colonic mucosa, bacteria are proposed to cross the epithelial layer by invading M cells overlaying lymphoid follicles, which allows them to reach the basolateral pole of epithelial cells where they induce their uptake. Entry into epithelial cells involves rearrangements of the cell cytoskeleton that extend beyond the zone of contact between the bacterium and the cell membrane, leading to membrane ruffling and engulfment of the bacterium within a vacuole. Once internalized by epithelial cells, bacteria rapidly lyse the membrane of the entry vacuole and gain access to the cell cytoplasm where they multiply with a generation time of approximately 40 min. By inducing actin polymerization at one of their poles, intracellular bacteria move within the cytoplasm of infected cells. This movement generates the formation of protrusions that contain one bacterium at their tip and are engulfed by adjacent epithelial cells, thereby allowing bacteria to disseminate from cell to cell without being exposed to the external milieu. Peptidoglycan fragments released by intracellular bacteria are detected by the Nod1 pathway, leading to phosphorylation and degradation of IkappaB, translocation of NF-kappaB to the nucleus and activation of NF-kappaB regulated genes. Analysis of the transcriptome of infected epithelial cells showed, in particular, increased expression of the gene encoding IL-8, a potent chemoattractant for neutrophils. Thus, epithelial cells actively participate in the detection and signaling of invasive bacteria to host defences. Bacteria released from M cells (after their initial uptake) or epithelial cells (after intracellular multiplication) interact with macrophages, escape from the phagocytic vacuole and induce apoptosis of infected cells. Apoptotic macrophages release pro-inflammatory cytokines, including IL-1 and IL-18, which, together with IL-8 released from infected epithelial cells, leads to recruitment of polymorphonuclear cells (PMN) at the site of infection. Transmigration of PMN destabilises the epithelial barrier and facilitates further invasion by luminal bacteria (Parsot, 2005). Although the molecular basis of shigellosis is complex, the initial step in pathogenesis is clearly bacterial invasion or penetration of the colonic mucosa. The resulting focus of Shigella infection is characterized by degeneration of the epithelium and by an acute inflammatory colitis in the lamina propria. Ultimately, desquamation and ulceration of the mucosa cause leakage of blood, inflammatory elements, and mucus into the intestinal lumen. Under these conditions the absorption of water by the colon is inhibited and the volume of stool is dependent upon the ileocecal flow. As a result, the patient will pass frequent, scanty, dysenteric stools (Hale, 1991).


        2. Incubation Period: Incubation period of the disease is 1-4 days which is usually followed by sudden onset of acute symptoms (Sur et al., 2004). Stool isolation of virulent S. flexneri 2a occurred as early as 18 hr following oral administration with an average of 2.6 days (DuPont et al., 1969).


        3. Prognosis: Combining the mortality calculated for all age groups, we estimate the total Shigella-related mortality among persons living in developing countries to be 1,093,505. In this estimate, children younger than 5 years are responsible for 61% of all Shigella-related deaths. The death rate due to Shigella in developed countries is exceedingly low. For example, the case-fatality rate during the 1980s was reported to be 0.4% in the USA and 0.05% in Israel, with an average of 0.2%. This means that approximately 3,030 of the 1,516,575 cases of shigellosis that occur in industrialized countries each year have a fatal outcome (Kotloff et al., 1999).


        4. Diagnosis Overview: Bacillary dysentery should be considered in any patient with acute diarrheal illness associated with toxemia and systemic symptoms, particularly when the illness lasts longer than 48 hours, if intrafamily spread occurs with an interval of 1 to 3 days between cases, if fever is present, and if blood or mucus is seen in stools (Dupont, 2005).


        5. Symptom Information :
          • Syndrome -- Shigellosis/Bacterial Dysentery:
            • Description: The first symptoms may be fever and abdominal cramping, followed by voluminous watery stool (these findings correlate with a small bowel site of infections), a decrease in fever, and an increase in the number of stools with smaller volume ("fractional stools"). In a day or two, bloody mucoid stools with fecal urgency and tenesmus may develop. These latter findings reflect a colonic site of infection. It is this evolution in disease symptoms, as the infecting strain descends the intestinal tract, that often leads to a clinical diagnosis of bacillary dysentery and may indicate the need for performing stool culture. Abdominal pain and diarrhea occur in nearly all patients with shigellosis, fever can be documented in approximately one third of cases, and mucus is seen in the stools of half and gross blood in 40% of the cases (Dupont, 2005). Shigellosis often begins with watery diarrhea accompanied by fever and abdominal cramps but may progress to classic dysentery with scant stools containing blood, mucus, and pus. Ulcerations, which are restricted to the large intestine and rectum, typically do not penetrate beyond the lamina propria. Bloodstream infections can occur but are rare. All four subgroups of Shigella are capable of causing dysentery, but S. dysenteriae serotype 1 has been associated with a particularly severe form of illness thought to be related to its production of Shiga toxin. Infection can also be asymptomatic, particularly infection with S. sonnei strains. Although these organisms are very important as causes of gastrointestinal infections, they rarely cause other types of infections. Complications of shigellosis include HUS, which is associated with S. dysenteriae 1 infection, and Reiter chronic arthritis syndrome, which is associated with S. flexneri infection. The identification of Shigella species is important for both clinical and epidemiologic purposes (Bopp et al., 2003).
            • Observed: We have estimated that each year 163.2 million episodes of endemic shigellosis occur in developing countries (3.5% of the population) and 1.5 million in industrialized countries (0.1% of the population). Approximately 1.1 million episodes (0.7%) result in death. Under-5-year-olds comprise the majority of cases (69%) and of fatal outcomes (61%) (Kotloff et al., 1999). The classical symptomatology of shigellosis, consisting of fever, abdominal pain, and diarrhea with dysentery, was seen in 12 (28%) of those challenged (DuPont et al., 1969).


              • Symptoms Shown in the Syndrome:

            • Fever:
              • Ontology: UMLS:C0015967
              • Description: Disease was defined as illness characterized by fever 100 F or higher (oral), severe abdominal cramping, diarrhea (at least 2 loose stools in a 24-hr period), or bloody mucoid stools (DuPont et al., 1969).
              • Observed: 58-100% (Guerrant et al., 2001). A febrile response was noted in 30% of the volunteers from 22 hr to 3 days after the administration of the virulent organisms (DuPont et al., 1969).
            • Abdominal Cramping:
              • Ontology: UMLS:C0000729
              • Observed: 75-100% (Guerrant et al., 2001). Ninety-three percent of the volunteers experienced abdominal pain or cramping, on the average, 3.6 days following challenge. The median time for developing abdominal pain was 2 days. This skewed distribution was due to 6 volunteers who complained of abdominal pain only after 8-12 days in association with their diarrhea and dysentery (DuPont et al., 1969).
            • Watery Stool:
              • Ontology: UMLS:C0232708
              • Description: The maximum number of stools produced by the volunteers in any given day postchallenge ranged from 1 to 24, with a mean of 8 per day (DuPont et al., 1969).
              • Observed: Sixty-three per cent developed diarrhea, on the average, after 4 days, with a median of 3 days postchallenge (DuPont et al., 1969).
            • Bloody Stool:
              • Ontology: UMLS:C1321898
              • Description: The changes in stool characteristics occurred later than other clinical features, with a mean of 7 days postchallenge (Dupont, 2005).
              • Observed: 25-51% (Guerrant et al., 2001). Blood was found in 42% and both blood and mucus were found in the stools of 37% (DuPont et al., 1969).
            • Mucoid Stool:
              • Ontology: UMLS:C0857147
            • Tenesmus:
              • Ontology: UMLS:C0232726
            • Vomiting and/or Nausea:
              • Ontology: UMLS:C0042963 C0027497
          • Syndrome -- Reiter's syndrome:
            • Description: Reiter's syndrome is the triad of arthritis, conjunctivitis and urethritis. The cause of the syndrome is unknown, though persons with the histocompatibility antigen HLA-B27 are clearly at greatly increased risk of Reiter's syndrome developing. In fact, up to 96 percent of affected patients are B27 positive, whereas only about 6 percent of Caucasian controls are positive. An infection, either urethritis or dysentery, usually triggers the syndrome in these susceptible persons, although some cases have no apparent preceding infectious episode. The infectious agent is unknown. In North America and England, Reiter's syndrome usually follows nongonococcal urethritis after sexual contact and occurs almost exclusively in young men. The syndrome may also be seen following infectious dysentery, usually shigellosis, particularly in continental Europe, the Mediterranean and Scandinavia. This dysenteric form also occurs primarily in young men but is also seen occasionally in children and women (Lehman, 1977). The arthritis preferentially involves the lower extremities, is asymmetric and frequently associated with a "sausage" digit (Barth and Segal, 1999). Agents causing infectious enteritis leading to reactive arthritis include certain strains of Salmonella, Shigella, Campylobacter and Yersinia (Barth and Segal, 1999).
            • Observed: Reiter's syndrome after dysentery appears to be rare in North America and England (Lehman, 1977).

        6. Treatment Information:
          • Azithromycin: Azithromycin, an azalide antibiotic, has significant activity against Gram-negative bacilli in vitro. It is more potent than erythromycin against members of the Enterobacteriaceae family, including Shigella spp. The intracellular concentrations of azithromycin achieved in colonic cells and leukocytes exceed serum concentrations by 100-fold or more. These properties suggest that azithromycin could be an option in the treatment of enteral infections caused by Shigella spp. In this sense one study that had included only adult patients with diarrhea showed that azithromycin exhibits an acceptable clinical and bacteriologic efficacy for shigellosis (Basualdo and Arbo, 2003). Inhibits RNA-dependent protein synthesis at the level of the 50S ribosome (Ehrenpreis and Ehrenpreis, 2001).
            • Applicable: Fluoroquinolones are not approved by the U.S. Food and Drug Administration (FDA) for use in children, and rifaximin is approved only for children 12 years and older. Therefore, azithromycin is the drug of choice for most children with traveler's diarrhea (Yates, 2005). Azithromycin is recommended as an alternative therapy by the American Academy of Pediatrics and the Infectious Diseases Society of America for treatment of shigellosis (Jain et al., 2005).
            • Contraindicator: Hypersensitivity to macrolide antibiotics (Ehrenpreis and Ehrenpreis, 2001).
            • Complication: Adverse reactions-Common: None. Adverse reactions-Severe: pseudomembranous colitis, ventricular arrhythmias, nephritis, cholestatic jaundice, angioedema (Ehrenpreis and Ehrenpreis, 2001).
            • Success Rate: A clinical success rate of 98% was observed for azithromycin compared with 78% for cefixime (P = 0.1). When bacteriologic efficacy was examined, azithromycin was clearly superior to cefixime (P less than 0.01) (Basualdo and Arbo, 2003). Only ceftrioxone and azithromycin are now clinically effective for the treatment of multi drug resistant shigellosis (Sur et al., 2004).
            • Drug Resistance: If azithromycin is to be used for empirical treatment of shigellosis, efforts to control the development of resistance to this agent are required. Without such efforts, it is likely that the organisms will develop resistance to azithromycin, just as occurred with so many other drugs once useful for the treatment of shigellosis and occurred when azithromycin was used to treat C. jejuni infections. Delaying the onset of resistance requires that the drug not be used for conditions for which antimicrobial therapy is not required or for conditions in which an older, less expensive, and narrower-spectrum agent might be used. Limiting the use of azithromycin requires the combined efforts of pharmaceutical companies that market the drug, practitioners who prescribe drugs, and governmental and nongovernmental organizations that play a major role in health care delivery in the poor countries where shigellosis is a major public health problem (Khan et al., 1997).
          • Cefixime: Binds to penicillin-binding proteins and disrupts or inhibits bacterial cell wall synthesis (Ehrenpreis and Ehrenpreis, 2001).
            • Applicable: The third generation cephalosporin cefixime has been reported to be effective in the treatment of shigellosis in children, although one study in adults with shigellosis found cefixime to be ineffective (Basualdo and Arbo, 2003).
            • Contraindicator: Hypersensitivity to other cephalosporins or related antibiotics, e.g., penicillin (Ehrenpreis and Ehrenpreis, 2001). Use with caution in patients with the following condition: kidney disease (Ehrenpreis and Ehrenpreis, 2001). Before use, determine if patient had previous hypersensitivity reaction to cephalosporins or penicillins. Incidence of cross-sensitivity to penicillins is 1-16%. A negative response to penicillin does not preclude allergic reaction to a cephalosporin (Ehrenpreis and Ehrenpreis, 2001).
            • Complication: Adverse reactions-Common: diarrhea, other GI symptoms. Adverse reactions-Serious: pseudomembranous colitis, hypersensitivity reactions, hepatitis, nephrotoxicity, bone marrow suppression, increased PT, seizures (Ehrenpreis and Ehrenpreis, 2001).
            • Success Rate: A clinical success rate of 98% was observed for azithromycin compared with 78% for cefixime (P = 0.1). When bacteriologic efficacy was examined, azithromycin was clearly superior to cefixime (P less than 0.01) (Basualdo and Arbo, 2003).
            • Drug Resistance: Of 369 isolates tested, 59% were resistant to TMP-SMZ, 63% were resistant to ampicillin, 1% were resistant to cefixime, and 0.3% were resistant to nalidixic acid; none of the isolates were resistant to ciprofloxacin (Replogle et al., 2000)
          • Ceftriaxone: Binds to penicillin-binding proteins and disrupts or inhibits bacterial cell wall synthesis (Ehrenpreis and Ehrenpreis, 2001).
            • Applicable:
            • Contraindicator: Hypersensitivity to other cephalosporins or related antibiotics, e.g., penicillin (Ehrenpreis and Ehrenpreis, 2001). Before use, determine if patient had previous hypersensitivity reaction to cephalosporins or penicillins. Incidence of cross-sensitivity to penicillins is 1-16%. A negative response to penicillin does not preclude allergic reaction to a cephalosporin (Ehrenpreis and Ehrenpreis, 2001).
            • Complication: Adverse reactions-Common: None. Adverse reactions-Serious: hepatitis, hypersensitivity reactions, pseudomembranous colitis, nephrotoxicity, bone marrow suppression, hemolytic anemia (Ehrenpreis and Ehrenpreis, 2001).
            • Success Rate: Only ceftrioxone and azithromycin are not clinically effective for the treatment of multi drug resistant shigellosis. However, ceftrioxone has to be administered parenterally and is expensive (Sur et al., 2004).
            • Drug Resistance: Resistance to ceftriaxone (both intermediate and resistant) among the S. sonnei strains was the highest ever reported. If we calculate the resistant strains only (2.4%), the rate is similar to those of Oregon and Israel. Resistance to ceftriaxone has rarely been reported among the developing countries. The S. flexneri strains were more resistant to ampicillin but less resistant to ceftriaxone than those of S. sonnei (Chuang et al., 2006).
          • Ciprofloxacin: Inhibits DNA gyrase, thereby blocking bacterial DNA replication (Ehrenpreis and Ehrenpreis, 2001).
            • Applicable: Reserve use of this drug for infections that are difficult to treat by other means (Ehrenpreis and Ehrenpreis, 2001).
            • Contraindicator: Hypersensitivity to fluoroquinolone antibiotics or quinolone antibiotics, e.g., cinoxacin, nalidixic acid (Ehrenpreis and Ehrenpreis, 2001). Safety and efficacy have not been established in children less than 18 years (Ehrenpreis and Ehrenpreis, 2001). Appears in breast milk. Potentially toxic to infant. Avoid breastfeeding (Ehrenpreis and Ehrenpreis, 2001).
            • Complication: Use with caution in patients with the following conditions: CNS disorders (epilepsy) (Ehrenpreis and Ehrenpreis, 2001). Rupture of Achilles and other tendons has occurred in patients taking fluoroquinolones. Serious and even fatal hypersensitivity reactions have occurred with these drugs, even after the first dose (Ehrenpreis and Ehrenpreis, 2001). Adverse reactions-Common: None. Adverse reactions-Serious: hypersensitivity reaction (anaphylaxis), seizures, pseudomembraneous colitis, cholestatic jaundice, renal failure, pulmonary edema, pulmonary embolism, cardiovascular collapse, pharyngeal edema (Ehrenpreis and Ehrenpreis, 2001).
            • Success Rate:
            • Drug Resistance: In the late 1980s, fluoroquinolones (norfloxacin, ciprofloxacin and ofloxacin) were introduced and were found to be very effective in the treatment of shigellosis cases, including those caused by multi drug resistant S. dysenteriae type 1 strain. Recent outbreak investigations in India (Siliguri, Diamond Harbour, Kolkata, and Aizwal) and Bangladesh showed high level of resistance even to norfloxacin, ciprofloxacin, and ofloxacin (Sur et al., 2004).
          • Levofloxacin: Inhibits DNA gyrase, thereby blocking bacterial DNA replication (Ehrenpreis and Ehrenpreis, 2001).
          • Norfloxacin: Inhibits DNA gyrase, thereby blocking bacterial DNA replication (Ehrenpreis and Ehrenpreis, 2001).
            • Applicable: Reserve use of this drug for infections that are difficult to treat by other means (Ehrenpreis and Ehrenpreis, 2001).
            • Contraindicator: Hypersensitivity to fluoroquinolone or quinolone antibiotics (Ehrenpreis and Ehrenpreis, 2001). Safety and efficacy have not been established in children less than 18 years (Ehrenpreis and Ehrenpreis, 2001). Likely to appear in breast milk. Potentially toxic to infant. Avoid breastfeeding (Ehrenpreis and Ehrenpreis, 2001). Use with caution in patients with CNS disorders (epilepsy), kidney disease (Ehrenpreis and Ehrenpreis, 2001).
            • Complication: Achilles and other tendon rupture have occurred in patients taking fluoroquinolones (Ehrenpreis and Ehrenpreis, 2001). Serious and fatal hypersensitivity reactions have occurred with these drugs, even after the first dose (Ehrenpreis and Ehrenpreis, 2001). Adverse reactions-Common: None. Adverse reactions-Serious: hypersensitivity reaction (anaphylaxis), seizures, pseudomembranous colitis, cholestatic jaundice, renal failure, pulmonary edema, pulmonary embolism, cardiovascular collapse, pharyngeal edema (Ehrenpreis and Ehrenpreis, 2001).
            • Drug Resistance: In the late 1980s, fluoroquinolones (norfloxacin, ciprofloxacin and ofloxacin) were introduced and were found to be very effective in the treatment of shigellosis cases, including those caused by multi drug resistant S. dysenteriae type 1 strain. Recent outbreak investigations in India (Siliguri, Diamond Harbour, Kolkata, and Aizwal) and Bangladesh showed high level of resistance even to norfloxacin, ciprofloxacin, and ofloxacin (Sur et al., 2004).
          • Trimethoprim-sulfamethoxazole:
            • Applicable: Trimethoprim-sulfamethoxazole had been the treatment of choice for this enteric infection, but resistance has become widespread for strains of Shigella (Dupont, 2005)
            • Contraindicator: Hypersensitivity to trimethoprim or sulfonamides, thiazide diuretics, oral hypoglycemics, megaloblastic anemia due to folate deficiency, pregnancy, lactation, treatment of streptococcal pharyngitis (Ehrenpreis and Ehrenpreis, 2001).
            • Complication: Adverse reactions-Common: anorexia, nausea, vomiting, glossitis, rash. Adverse reactions-Serious: Stevens-Johnson syndrome (rare), pseudomembranous colitis, agranulocytosis, aplastic anemia, megaloblstic anemia, hyperkalemia, hemolysis (patients with G6PD deficiency) (Ehrenpreis and Ehrenpreis, 2001).
            • Drug Resistance: Antimicrobial resistance has complicated the selection of empirical agents for treatment of shigellosis, particularly in children. When the prevalence of resistance to ampicillin among Shigella isolates increased in the 1970s, trimethoprim-sulfamethoxazole (TMP-SMX) became the alternative. In 1986, national laboratory-based surveillance for antimicrobial susceptibility of Shigella isolates revealed that 32% were resistant to ampicillin and 7% were resistant to TMP-SMX. In 1995, laboratory-based surveillance demonstrated resistance to ampicillin in 67% and resistance to TMP-SMX in 35% of Shigella isolates. More recent data from Oregon revealed high rates of TMP-SMX (63%), ampicillin (59%), and multidrug (13%) resistance among Shigella isolates from this state (Sivapalasingam et al., 2006). With 63% of our isolates resistant to ampicillin and 59% resistant to TMP-SMZ, Oregon Shigella isolates resemble those reported from Brazil, Bangladesh, and Thailand (Replogle et al., 2000).
          • Intravenous fluid replacement: In certain patients with bacillary dysentery (particularly infants and older adult patients), significant dehydration may result from excessive fluid loss through diarrhea and vomiting. The fluid losses can generally be replaced by oral intake because the diarrhea associated with bacillary dysentery is not normally associated with profound fluid and electrolyte depletion. If vomiting or extreme toxemia is a prominent feather of the illness, especially in the very young or the very old, intravenous fluid replacement may be necessary (Dupont, 2005).

    4. Prevention:
      1. Hygiene:
        • Ontology: UMLS:C0020405
        • Description: The most important aspect in control of diarrheal disease is hygiene, both general and personal. General issues deal with clean water, clean food, and appropriate sanitation facilities. Despite the high-quality water and food supplies available in the United States and other socioeconomically developed areas of the world, outbreaks of foodborne and waterborne disease continue to occur, generally due to improper handling and storage of food. Personal measures include careful personal hygiene, especially handwashing, and limited use of antacids, antimotility drugs, and antimicrobial agents. Promotion of handwashing has proven to be a highly effective measure in decreasing the incidence of diarrhea among people living in high-risk areas, such as settlements in Pakistan. Appropriate diaper-changing facilities and techniques should be available and implemented in childcare facilities. Breastfeeding in all areas of the world should be promoted, implemented, and supported (O'Ryan et al., 2005). Since the main route of transmission of shigellosis is through water, food and also person-to-person contact, the prevention and control strategies essentially include provision of safe water supply and adequate sanitation facilities, maintenance of good personal hygiene and food safety. Hand washing with plenty of water and soap is the most important single effective preventive strategy against shigellosis. It is emphasized that hands should be washed before eating, before feeding children, after defecation and after disposal of children's excreta. These measures are further reinforced in epidemic situations, when because of the very low infective dose of the organism and its potential for rapid spread, stringent control measures need to be instituted through simple but effective health education messages to the common masses (Sur et al., 2004).
        • Efficacy:
          • Rate: Children younger than 5 years in households that received plain soap and handwashing promotion had a 50% lower incidence of pneumonia than controls (95% CI (-65% to -34%). Also compared with controls, children younger than 15 years in households with plain soap had a 53% lower incidence of diarrhoea (-65% to -41%) and a 34% lower incidence of impetigo (-52% to -16%). Incidence of disease did not differ significantly between households given plain soap compared with those given antibacterial soap (Luby et al., 2005). Compared with control neighborhoods, children living in households that received plain soap and handwashing promotion were 56% less likely to visit a health care practitioner for diarrhea (95% CI, -69% to -43%). Hospitalization for diarrhea was uncommon, occurring in only 0.23% of the observed person-weeks. Children living in households receiving plain soap and handwashing promotion were 26% less likely to be hospitalized for diarrhea but this difference was not statistically significant (95% CI, -100% to 66%). Only 5% of observed episodes of diarrhea were persistent diarrhea (ie, episodes lasting more than 14 days). Children living in households receiving plain soap and handwashing promotion were 31% less likely to have a persistent episode of diarrhea but this difference was not statistically significant (95% CI, -70% to 8%). The probability of visiting a health care practitioner for diarrhea, being hospitalized for diarrhea, and having a persistent episode of diarrhea was similar among households receiving antibacterial soap vs households receiving plain soap (Luby et al., 2004)

    5. Model System:
      1. Guinea pig:
        1. Ontology: UMLS:C0999699
        2. Model Host: Male Sprague-Dawley guinea pigs (McKenzie et al., 2005)
        3. Model Pathogens:
        4. Description: Oral challenge of starved, opiated guinea pigs with S. flexneri 2A first established the invasive nature of Shigella infections (Hale, 1991). Two weeks following vaccination, the 30 guinea pigs were challenged in the conjunctival sac with virulent S. sonnei. Within 3 days all 20 eyes in the 10 animals in the PBS group were inflamed. During the 6 days after challenge none of the 20 animals in the whole-cell vaccine (SsWC) groups (with or without LTR192G) developed inflammation, demonstrating a 100% protection rate (McKenzie et al., 2005). LTR(192G) [is] a mucosal adjuvant made from the heat-labile toxin of enterotoxigenic E. coli by a single amino acid substitution within the subtended disulfide region of the A subunit (McKenzie et al., 2005).
      2. Mouse:
        1. Ontology: UMLS:C0025929
        2. Model Host: BALB/c mice (Charles River) (Martino et al., 2005)
        3. Model Pathogens:
          • Shigella flexneri 5 . After a 6-h starvation period, mice were infected ig by a polyethylene feeding tube with cfu of S. flexneri 5a strain M90T SmR or strain BS176 Sm R in 100 m L of sodium bicarbonate (1.4%) (Martino et al., 2005).
        4. Description: In this study, we addressed 3 key hypotheses about the inability of mice to develop shigellosis. First, we examined whether the endogenous flora could protect the intestinal tissue from Shigella infection. We found that treatment of mice with Sm is a prerequisite for colonization of the intestinal tract by shigellae, which is in accordance with the role played by the intestinal flora in preventing oral infection with various enteropathogens, such as Salmonella species. Then, we investigated the ability of Shigella species to invade the intestinal tissue. As in humans, the colon and eventually the cecum of the Sm-treated mice were the main targets for the invasion of a wild-type Shigella strain. However, in contrast to human shigellosis, no lesions or only a few abscesses were observed in the mice, despite the presence of a high number of shigellae. Finally, we considered the hypothesis that the murine epithelium may be unable to respond to intracellular shigellae by recruiting an inflammatory infiltrate. Interestingly, the presence of a mononuclear infiltrate and a dramatic expansion of lymphoid follicles dispersed along the CM and the cecal mucosa were the main features of the infected intestine, thus demonstrating that the intestinal epithelium is able to sense shigellae and to mount an inflammatory reaction. However, in contrast to the situation in human shigellosis, and in accordance with the paucity of lesions observed, a moderate number of PMNLs was observed in the mice (Martino et al., 2005).
      3. Mouse:
        1. Ontology: UMLS:C0025929
        2. Model Host: Newborn BALB/c mice (Janvier) (Fernandez et al., 2003).
        3. Model Pathogens:
          • Shigella flexneri 5 . Two S. flexneri strains were used in this study: M90T, an invasive isolate belonging to serotype 5a; and BS176, its isogenic, non-invasive derivative that has been cured of the virulence plasmid, pWR100 (Fernandez et al., 2003). Mice were separated from their mothers 2 h before the experiment and then inoculated i.g. with 50 ul of the bacterial suspension (Fernandez et al., 2003).
        4. Description: Shigella infection is characterized by the induction of acute inflammation, which is responsible for the massive tissue destruction of the intestinal mucosa. A murine model would be a valuable tool for gaining a better understanding of the physiopathology of shigellosis and the host immune response to Shigella infection, but adult mice do not develop disease upon oral inoculation. We therefore attempted to develop a model of infection in newborn mice. Four-day-old mice inoculated with 50 ul of 5 x 10(9) invasive wild-type Shigella flexneri 5a were susceptible to bacterial infection, but mice inoculated with the non-invasive strain BS176 were not. Histologically, 4-day-old mice infected with the invasive strain presented intestinal lesions and inflammation similar to those described in patients with shigellosis. Moreover, cytokine and chemokine responses consistent with inflammation were observed. Lower bacterial inocula induced less severe intestinal damage. In contrast, 5-day-old mice inoculated with either the invasive or the non-invasive strain were not infected. We have thus established a mouse model that is suitable for the study of the pathogenesis of intestinal Shigella infection (Fernandez et al., 2003).
      4. Rabbit:
        1. Ontology: UMLS:C0034493
        2. Model Host: New Zealand White rabbits (D'Hauteville et al., 2002)
        3. Model Pathogens:
        4. Description: Injection of shigellae into ligated rabbit ileal loops has been used as a model for bacterial invasion which elicits fluid secretion (Hale, 1991). A total of 16 New Zealand White rabbits weighing 2.5-3 kg (Charles River Breeding Laboratories, Wilmington, MA) were used for experimental infections. From each of these animals, nine intestinal ligated loops, each of 5 cm, were prepared, as previously described. Within each loop, 109 bacteria were injected in 0.5 ml of isotonic saline. Following 8 h of infection, animals were sacrificed (D'Hauteville et al., 2002).
      5. Rat:
        1. Ontology: UMLSC0034693
        2. Model Host: Wistar rats (Rene et al., 2005)
        3. Model Pathogens:
        4. Description: With the aim of setting up an animal model of Shigella dysenteriae-induced diarrhea, Wistar rats received per os increasing densities of S. dysenteriae type 1 (Sd1). Inoculum of 12 x 10(8) Sd1 provoked dysenteric diarrhea within 24 h. Feces of healthy rats were molded, brown to black and rough. Rats developing diarrhea presented blood at the anal orifice; stools were soft or liquid containing mucus, or molded, smooth and mucus-coated. At times, stools appeared longer, dark and shiny due to the presence of mucus and blood, or molded, lumpy and brittle. Diarrheal induction was associated with abdominal ailment, progressive increase in stool weight and frequency, and increase in bacterial population. Sixty-seven percent of the total number of deaths had occurred by day 6 after diarrheal induction. These results indicate that Sd1 induced in rats a model of shigellosis which might be helpful for physiopathological and pharmacological studies of this type of infectious diarrhea (Rene et al., 2005).
      6. Rhesus macaques:
        1. Ontology: UMLS:C0024400
        2. Model Host:
        3. Model Pathogens:
        4. Description: Oral challenge of rhesus monkeys, which are susceptible to naturally acquired Shigella infections, confirmed the invasive pathogenic mechanism (Hale, 1991).
  2. Other Primates:
    1. Taxonomy Information:
      1. Species:
        1. Ateles geoffroyi robustus :
          • Ontology: UMLS:C0999511
          • GenBank Taxonomy No.: 118645
          • Scientific Name: Ateles geoffroyi robustus (NCBI Taxonomy)
          • Description: Data were collected from primate groups with enzootic shigellosis and included the following species: white-cheeked and siamong gibbons (Hylobates concolor and H syndactylies); lion-tailed, celebes, and Barbary macaques (Macaca silenus, M nigera [sic], and M sylvanus); black and white colobus monkeys (Colobus guerzea [sic]); grey-cheeked mangabeys (Cerecocebus albigena); spider monkeys (Ateles susciceps robustus); ruffed lemurs (Lemur varrigatus); lowland gorillas (Gorilla gorilla); and orangutans (Pongo pygmaeus) (Banish et al., 1993). Shigella sonnei was isolated from feces of grey-cheeked mangabeys, celebes macaques, and spider monkeys (Banish et al., 1993).
        2. Baboon :
          • Ontology: UMLS:C0030362
          • GenBank Taxonomy No.: 9554
          • Scientific Name: Papio (NCBI Taxonomy)
          • Description: Cultural surveys for shigellae have been made in 3 ecological groups of baboons: 1) wild, 2) newly imported, and 3) captive-residential. Preliminary storage of rectal swabs from wild baboons in transport media for several weeks may have accounted for the virtual lack of recovery of Shigella isolates. The percentage of baboons shedding shigellae in the newly-imported and captive animals was practically identical (37.8% and 35.0%, respectively), but the incidence of S. flexneri was higher in the latter group, 27.5% as opposed to 18.9% in the newly imported group. In the latter, presumed S. sonnei accounted for most of the other isolates. However, cultures which were thought to be S. sonnei on a biochemical basis, agglutinated weakly or not at all in the corresponding antiserum. There were a few isolates of S. boydii and others which cross-reacted with both S. boydii and S. dysenteriae poly-antisera. S. flexneri, serotype 1-a, was predominant in captive baboons which were clinically well. A few animals showing diarrhea also yielded this serotype (Pinkerton, 1968).
        3. Barbary ape :
          • Ontology: UMLS:C0004741
          • GenBank Taxonomy No.: 9546
          • Scientific Name: Macaca sylvanus (NCBI Taxonomy)
          • Description: On 15 February 2004 an episode of bloody diarrhea affecting a barbary macaque (Macaca sylvanus) occurred at the Vienna Zoo in Austria. Despite prompt initiation of therapy (enrofloxacin, 50 mg qd p.o. plus metronidazole, 50 mg bid p.o.) and implementing quarantine measures for the diseased animals, a total of four of the ten monkeys fell ill and died; one within 30 hours, a second and third after seven days and the fourth after two weeks. Two intestinal samples obtained during post-mortem examination yielded Shigella flexneri Sv 2a (Lederer et al., 2005).
        4. Black-and-red tamarin :
          • Ontology: UMLS:C0324808
          • GenBank Taxonomy No.: 9489
          • Scientific Name: Saguinus nigricollis (NCBI Taxonomy)
          • Description: An outbreak of shigellosis due to Shigella sonnei is reported in laboratory maintained marmosets (Callithrix jacchus) and tamarins (Saguinus nigricollis) (Cooper and Needham, 1976).
        5. Black spider monkey :
          • Ontology: UMLS:C0999512
          • GenBank Taxonomy No.: 9510
          • Scientific Name: Ateles paniscus (NCBI Taxonomy)
          • Description: An epizootic of shigellosis occurred in a monkey colony 8 months after arrival of an unsuspected carrier monkey. The infection spread rapidly to 80 monkeys, ranging in age from a few months to 8 years. The entire colony was affected (Mannheimer and Rubin, 1969). Species represented were Alouatta villosa, Aotus trivirgatus, Ateles belzebuth, Ateles geoffroyi, Ateles paniscus, Cacajao rubicundus, Cebus albifrons, Cebus apella, Cebus capucinus, Cebus griseus, Cynopithecus niger, Hylobates lar, Hylobates moloch, Lagothrix cana, Lagothrix lagothricha, Macaca mulatta, Macaca speciosa, Pithecia monachus, and Symphalangus syndactylus (Mannheimer and Rubin, 1969).
        6. Brown capuchin :
          • Ontology: UMLS:C0999514
          • GenBank Taxonomy No.: 9515
          • Scientific Name: Cebus apella (NCBI Taxonomy)
          • Description: An epizootic of shigellosis occurred in a monkey colony 8 months after arrival of an unsuspected carrier monkey. The infection spread rapidly to 80 monkeys, ranging in age from a few months to 8 years. The entire colony was affected (Mannheimer and Rubin, 1969). Species represented were Alouatta villosa, Aotus trivirgatus, Ateles belzebuth, Ateles geoffroyi, Ateles paniscus, Cacajao rubicundus, Cebus albifrons, Cebus apella, Cebus capucinus, Cebus griseus, Cynopithecus niger, Hylobates lar, Hylobates moloch, Lagothrix cana, Lagothrix lagothricha, Macaca mulatta, Macaca speciosa, Pithecia monachus, and Symphalangus syndactylus (Mannheimer and Rubin, 1969).
        7. Cacajao rubicundus :
          • Ontology: UMLS:xxx, GO:xxx, SNOMED:xxx, otherStd:xxx
          • GenBank Taxonomy No.: 70927
          • Scientific Name: Cacajao rubicundus (NCBI Taxonomy)
          • Description: An epizootic of shigellosis occurred in a monkey colony 8 months after arrival of an unsuspected carrier monkey. The infection spread rapidly to 80 monkeys, ranging in age from a few months to 8 years. The entire colony was affected (Mannheimer and Rubin, 1969). Species represented were Alouatta villosa, Aotus trivirgatus, Ateles belzebuth, Ateles geoffroyi, Ateles paniscus, Cacajao rubicundus, Cebus albifrons, Cebus apella, Cebus capucinus, Cebus griseus, Cynopithecus niger, Hylobates lar, Hylobates moloch, Lagothrix cana, Lagothrix lagothricha, Macaca mulatta, Macaca speciosa, Pithecia monachus, and Symphalangus syndactylus (Mannheimer and Rubin, 1969).
        8. Celebes crested macaque :
          • Ontology: UMLS:C0205802
          • GenBank Taxonomy No.: 54600
          • Scientific Name: Macaca nigra (NCBI Taxonomy)
          • Description: Stool specimens collected systematically from a group of Celebes black macaques (Macaca nigra) with a high incidence of diarrhea were examined microbiologically. Numerous isolates of Shigella flexneri, Campylobacter jejuni and pathogenic Escherichia coli were recovered (Olson et al., 1986).
        9. Chimpanzee :
          • Ontology: UMLS:C0008111
          • GenBank Taxonomy No.: 9598
          • Scientific Name: Pan troglodytes (NCBI Taxonomy)
          • Description: Shigellosis due to Shigella dysenteriae was diagnosed in an adult male captive chimpanzee (Pan troglodytes) which died suddenly after a brief recovery from illness lasting at least 3 wk. Confirmatory diagnosis was based on postmortem examination and cultural isolation of Shigella dysenteriae from the intestine, liver, lung, spleen and heart blood (Enurah et al., 1988).
        10. Common gibbon :
          • Ontology: UMLS:xxx, GO:xxx, SNOMED:xxx, otherStd:xxx
          • GenBank Taxonomy No.: 9580
          • Scientific Name: Hylobates lar (NCBI Taxonomy)
          • Description: Another infant wooly monkey (L. lagothricha), 2 gibbons (H. lar and H. moloch), and 1 siamang (S. syndactylus) were found to have diarrhea (Mannheimer and Rubin, 1969). Bacteriologic tests of the cultured pathogens confirmed the presumptive diagnosis of March 19-shigellosis caused by Shigella flexneri of mixed types (Mannheimer and Rubin, 1969).
        11. Common squirrel monkey, South American squirrel monkey :
          • Ontology: UMLS:C0999517
          • GenBank Taxonomy No.: 9521
          • Scientific Name: Saimiri sciureus (NCBI Taxonomy)
          • Description: Two weeks after acquisition, a young male squirrel monkey was presented for a sanitary control at the Clinica Exotics (Barcelona, Spain). It was estimated to be two years old, and weighed 725 g (normal range 700-1100 g as reported by Lehner 1984). Clinical examination revealed diarrhoea, which the owners reported was intermittent; later, it was indicated that the squirrel monkey colony from which this animal originated was experiencing an outbreak of diarrhoea. The animal also had foci of alopecia in the tail and hind limbs and its body condition was fair (Juan-Salles et al., 1999). Shigella species was isolated from the rectal swab but the plates were destroyed by the laboratory so further characterization of the isolate was not possible (Juan-Salles et al., 1999).
        12. Common woolly monkey :
          • Ontology: UMLS:xxx, GO:xxx, SNOMED:xxx, otherStd:xxx
          • GenBank Taxonomy No.: 9519
          • Scientific Name: Lagothrix lagotricha (NCBI Taxonomy)
          • Description: Another infant wooly monkey (L. lagothricha), 2 gibbons (H. lar and H. moloch), and 1 siamang (S. syndactylus) were found to have diarrhea (Mannheimer and Rubin, 1969). Bacteriologic tests of the cultured pathogens confirmed the presumptive diagnosis of March 19-shigellosis caused by Shigella flexneri of mixed types (Mannheimer and Rubin, 1969).
        13. Douroucouli, Owl monkey :
          • Ontology: UMLS:xxx, GO:xxx, SNOMED:xxx, otherStd:xxx
          • GenBank Taxonomy No.: 9505
          • Scientific Name: Aotus trivirgatus (NCBI Taxonomy)
          • Description: A number of other bacteria, some of which are pathogenic for man, have been isolated from the owl monkey. These include Salmonella enteriditis ser Gyphimurium, S. enteriditis ser Flint, Shigella sonnei, Yersinia enterocolitica, Streptococcus, and Staphylococcus (Daniel et al., 1976).
        14. Lowland gorilla :
          • Ontology: UMLS:C0324857
          • GenBank Taxonomy No.: 9595
          • Scientific Name: Gorilla gorilla gorilla (NCBI Taxonomy)
          • Description: A male western lowland gorilla (Gorilla gorilla gorilla) born at the Cincinnati Zoo arrived at the Pittsburgh Zoo at age 17 mo. The animal had episodic diarrhea, anorexia, lethargy, lameness, fever, and leukocytosis since 6 mo of age. Cultures of diarrheic feces at age 15 and 16 mo yielded Shigella sp. Type B (presumed flexneri). Lameness occurred at 15 and 16 mo and affected the right hand and wrist, and left foot, respectively. Complete blood count (CBC) revealed primarily a neutrophilic leukocytosis, although an absolute monocytosis and anemia were each noted once. Serum biochemical analysis revealed hypoalbuminemia, although decreased electrolyte levels were detected during one diarrheic episode. Whereas some episodes resolved on their own, most were treated with the nonsteroidal anti-inflammatory sulindac (Clinoril, Merck and Co., Inc., West Point, Pennsylvania 19486, USA; 5 mg/kg p.o. as needed) and/or oral antibiotics. After the isolation of Shigella sp. from the feces, treatment with cefixime (Suprax oral susp., Lederle Laboratories, Pearl River, New York 10965, USA; 4 mg/kg p.o. b.i.d. for 7 days) was prescribed. Fecal culture performed 2 wk prior to the animal's transfer was negative for enteric pathogens (Neiffer et al., 2000).
        15. Gray-cheeked mangabey :
          • Ontology: UMLS:C0324835
          • GenBank Taxonomy No.: 75567
          • Scientific Name: Lophocebus albigena (NCBI Taxonomy)
          • Description: Shigella sonnei was isolated from feces of grey-cheeked mangabeys, spider monkeys, and celebes macaques (Banish et al., 1993). Synonym: Cercocebus albigena (NCBI Taxonomy).
        16. Guatemala howler monkey :
          • Ontology: UMLS:xxx, GO:xxx, SNOMED:xxx, otherStd:xxx
          • GenBank Taxonomy No.: 182253
          • Scientific Name: Alouatta pigra, Alouatta villosa pigra (NCBI Taxonomy)
          • Description: An epizootic of shigellosis occurred in a monkey colony 8 months after arrival of an unsuspected carrier monkey. The infection spread rapidly to 80 monkeys, ranging in age from a few months to 8 years. The entire colony was affected (Mannheimer and Rubin, 1969). Species represented were Alouatta villosa, Aotus trivirgatus, Ateles belzebuth, Ateles geoffroyi, Ateles paniscus, Cacajao rubicundus, Cebus albifrons, Cebus apella, Cebus capucinus, Cebus griseus, Cynopithecus niger, Hylobates lar, Hylobates moloch, Lagothrix cana, Lagothrix lagothricha, Macaca mulatta, Macaca speciosa, Pithecia monachus, and Symphalangus syndactylus (Mannheimer and Rubin, 1969).
        17. Guereza, Eastern black-and -white colobus :
          • Ontology: UMLS:C0598112
          • GenBank Taxonomy No.: 33548
          • Scientific Name: Colobus guereza (NCBI Taxonomy)
          • Description: An epizootic of shigellosis in the primate population developed at the National Zoological Park (NZP) in 1984 and subsequently S. flexneri became enzootic. Species known to have been infected included white-cheeked and siamang gibbons (Hylobates concolor and H. syndactylies [sic]); lion-tailed, celebes, and Barbary macaques (Macaca silenus, M nigera [sic], and M. sylvanus); black and white colobus monkeys (Cologus guerzea [sic]); and lowland gorillas (Gorilla gorilla) (Banish et al., 1993).
        18. Hanuman langur :
          • Ontology: UMLS:C1038886
          • GenBank Taxonomy No.: 9574
          • Scientific Name: Presbytis entellus (NCBI Taxonomy)
          • Description: Shigella species have been isolated only rarely from the two species of langur, P. entellus and P. crisatus, perhaps owing to their unique digestive tract, which includes a compartmented stomach (Good et al., 1969).
        19. Liontailed macaque :
          • Ontology: UMLS:C0324830
          • GenBank Taxonomy No.: 54601
          • Scientific Name: Macaca silenus (NCBI Taxonomy)
          • Description: Shignella flexneri was isolated from feces of gibbons and lion-tailed macaques (Banish et al., 1993).
        20. Presbytis cristata :
          • Ontology: UMLS:C0324821
          • GenBank Taxonomy No.: 36232
          • Scientific Name: Presbytis cristata (NCBI Taxonomy)
          • Description: Shigella species have been isolated only rarely from the two species of langur, P. entellus and P. crisatus, perhaps owing to their unique digestive tract, which includes a compartmented stomach (Good et al., 1969).
        21. Orangutan :
          • Ontology: UMLS:C0032638
          • GenBank Taxonomy No.: 9600
          • Scientific Name: Pongo pygmaeus (NCBI Taxonomy)
          • Description: On 19 February a 6-year-old female orangutan (Pongo pygmaeus) developed fatigue with onset of bloody diarrhea 24 hours later and died after a further 24 hours. On 22 February an 18-year-old orangutan developed weakness and hemorrhagic discharge 24 hours after delivering a clinically healthy offspring. Four hours later the animal died despite intensive care. Both animals showed hemorrhagic, necrotizing colitis and peritonitis when sectioned. Stool specimens from the two cadavers and from the three remaining orangutans (the male developed bloody diarrhea on 24 February) yielded Shigella flexneri SV 2a. The two adult animals were treated with ciprofloxacin (400 mg q12h i.v.), the asymptomatic newborn with mecillinam (50 mg per day, in three doses, i.v., for eight days) (Lederer et al., 2005).
        22. Pithecia monachus :
          • Ontology: UMLS:xxx, GO:xxx, SNOMED:xxx, otherStd:xxx
          • Scientific Name: Pithecia monachus (Mannheimer and Rubin, 1969)
          • Description: An epizootic of shigellosis occurred in a monkey colony 8 months after arrival of an unsuspected carrier monkey. The infection spread rapidly to 80 monkeys, ranging in age from a few months to 8 years. The entire colony was affected (Mannheimer and Rubin, 1969). Species represented were Alouatta villosa, Aotus trivirgatus, Ateles belzebuth, Ateles geoffroyi, Ateles paniscus, Cacajao rubicundus, Cebus albifrons, Cebus apella, Cebus capucinus, Cebus griseus, Cynopithecus niger, Hylobates lar, Hylobates moloch, Lagothrix cana, Lagothrix lagothricha, Macaca mulatta, Macaca speciosa, Pithecia monachus, and Symphalangus syndactylus (Mannheimer and Rubin, 1969).
        23. Rhesus monkey :
          • Ontology: UMLS:xxx, GO:xxx, SNOMED:xxx, otherStd:xxx
          • GenBank Taxonomy No.: 9544
          • Scientific Name: Macaca mulatta (NCBI Taxonomy)
          • Description: The 21 fatal cases in infant rhesus monkeys included 6 cases (29%) of shigellosis (Shigella flexneri 4), 2 (10%) of salmonellosis, 23 (57%) in which no enteric pathogens were isolated, and 1 case in which colonic contents inadvertently were not cultured (Padovan and Cantrell, 1983).
        24. Stump-tail macaque :
          • Ontology: UMLS:xxx, GO:xxx, SNOMED:xxx, otherStd:xxx
          • GenBank Taxonomy No.: 9553
          • Scientific Name: Macaca speciosa (NCBI Taxonomy)
          • Description: An epizootic of shigellosis occurred in a monkey colony 8 months after arrival of an unsuspected carrier monkey. The infection spread rapidly to 80 monkeys, ranging in age from a few months to 8 years. The entire colony was affected (Mannheimer and Rubin, 1969). Species represented were Alouatta villosa, Aotus trivirgatus, Ateles belzebuth, Ateles geoffroyi, Ateles paniscus, Cacajao rubicundus, Cebus albifrons, Cebus apella, Cebus capucinus, Cebus griseus, Cynopithecus niger, Hylobates lar, Hylobates moloch, Lagothrix cana, Lagothrix lagothricha, Macaca mulatta, Macaca speciosa, Pithecia monachus, and Symphalangus syndactylus (Mannheimer and Rubin, 1969).
        25. Siamang :
          • Ontology: UMLS:C0086979
          • GenBank Taxonomy No.: 9590
          • Scientific Name: Symphalangus syndactylus, Hylobates syndactylus (NCBI Taxonomy)
          • Description: An epizootic of shigellosis in the primate population developed at the National Zoological Park (NZP) in 1984 and subsequently S. flexneri became enzootic. Species know to have been infected included white-cheeked and siamang gibbons (Hylobates concolor and H. syndactylies [sic]) (Banish et al., 1993). From 1984, 2 species in particular, the endangered white-cheeked and siamang gibbons had a high incidence (mean of 50%/y, n = 12 to 14) of infection and illness, with the deaths of 2 breeding females (Banish et al., 1993).
        26. Silvery gibbon :
          • Ontology: UMLS:xxx, GO:xxx, SNOMED:xxx, otherStd:xxx
          • GenBank Taxonomy No.: 81572
          • Scientific Name: Hylobates moloch (NCBI Taxonomy)
          • Description: Another infant wooly monkey (L. lagothricha), 2 gibbons (H. lar and H. moloch), and 1 siamang (S. syndactylus) were found to have diarrhea (Mannheimer and Rubin, 1969). Bacteriologic tests of the cultured pathogens confirmed the presumptive diagnosis of March 19-shigellosis caused by Shigella flexneri of mixed types (Mannheimer and Rubin, 1969).
        27. White-bellied spider monkey :
          • Ontology: UMLS:C0999509
          • GenBank Taxonomy No.: 9507
          • Scientific Name: Ateles belzebuth (NCBI Taxonomy)
          • Description: An epizootic of shigellosis occurred in a monkey colony 8 months after arrival of an unsuspected carrier monkey (Mannheimer and Rubin, 1969) The carrier and a cagemate, both female spider monkeys (A. belzebuth) were received in June, 1968, at an estimated age of 8 months (Mannheimer and Rubin, 1969). The infection spread rapidly to 80 monkeys, ranging in age from a few months to 8 years; the entire colony was affected (Mannheimer and Rubin, 1969).
        28. White-cheeked gibbon :
          • Ontology: UMLS:C0324849
          • Scientific Name: Hylobates concolor (Banish et al., 1993)
          • Description: An epizootic of shigellosis in the primate population developed at the National Zoological Park (NZP) in 1984 and subsequently S. flexneri became enzootic. Species know to have been infected included white-cheeked and siamang gibbons (Hylobates concolor and H. syndactylies [sic]) (Banish et al., 1993). From 1984, 2 species in particular, the endangered white-cheeked and siamang gibbons had a high incidence (mean of 50%/y, n = 12 to 14) of infection and illness, with the deaths of 2 breeding females (Banish et al., 1993).
        29. White-faced sapajou :
          • Ontology: UMLS:xxx, GO:xxx, SNOMED:xxx, otherStd:xxx
          • GenBank Taxonomy No.: 9516
          • Scientific Name: Cebus capucinus (NCBI Taxonomy)
          • Description: An epizootic of shigellosis occurred in a monkey colony 8 months after arrival of an unsuspected carrier monkey. The infection spread rapidly to 80 monkeys, ranging in age from a few months to 8 years. The entire colony was affected (Mannheimer and Rubin, 1969). Species represented were Alouatta villosa, Aotus trivirgatus, Ateles belzebuth, Ateles geoffroyi, Ateles paniscus, Cacajao rubicundus, Cebus albifrons, Cebus apella, Cebus capucinus, Cebus griseus, Cynopithecus niger, Hylobates lar, Hylobates moloch, Lagothrix cana, Lagothrix lagothricha, Macaca mulatta, Macaca speciosa, Pithecia monachus, and Symphalangus syndactylus (Mannheimer and Rubin, 1969).
        30. White-fronted capuchin :
          • Ontology: UMLS:xxx, GO:xxx, SNOMED:xxx, otherStd:xxx
          • GenBank Taxonomy No.: 9514
          • Scientific Name: Cebus albifrons (NCBI Taxonomy)
          • Description: On March 19, monkey 1, a 6-year-old female capuchin (C. albifrons) weighing 5 lb. and housed in cage room 1 developed nystagmus, muscular tremors, and diarrhea. She was promptly removed from the room to an isolation cage. The presumptive diagnosis was shigellosis (Mannheimer and Rubin, 1969). Bacteriologic tests of the cultured pathogens confirmed the presumptive diagnosis of March 19-shigellosis caused by Shigella flexneri of mixed types (Mannheimer and Rubin, 1969).
        31. White-tufted-ear marmoset :
          • Ontology: UMLS:C0006765
          • GenBank Taxonomy No.: 9483
          • Scientific Name: Callithrix jacchus (NCBI Taxonomy)
          • Description: An outbreak of shigellosis due to Shigella sonnei is reported in laboratory maintained marmosets (Callithrix jacchus) and tamarins (Saguinus nigricollis) (Cooper and Needham, 1976).

    2. Infection Process:

      No infection process information is currently available here.

    3. Disease Information:

      No disease information is currently available here.

    4. Prevention:

      No prevention information is currently available here.

    5. Model System:

      No model system information is currently available here.

  3. Carnivora:
    1. Taxonomy Information:
      1. Species:
        1. Dog :
          • Ontology: UMLS:C0012984
          • GenBank Taxonomy No.: 9615
          • Scientific Name: Canis familiaris (NCBI Taxonomy)
          • Description: One survey of 278 dogs resulted in the recovery of a single Shigella species from 1 animal; another survey of 54 dogs resulted in no recovery (Butler and Herd, 1965). The infection rate of 0.5 per cent among 400 dogs reported in this study is the same as that of Floyed (1955) who isolated five shigellae from 1000 dogs in Cairo (Khan, 1968).
        2. Cat :
          • Ontology: UMLS:C0007450
          • GenBank Taxonomy No.: 9685
          • Scientific Name: Felis catus (NCBI Taxonomy)
          • Description: During a survey of Salmonella infection of animals in the Sudan, Shigella were isolated from a chimpanzee, two dogs and a cat (Khan, 1968). The intestinal tracts of the other dog and cat from which Sh. sonnei was isolated were apparently normal (Khan, 1968).

    2. Infection Process:

      No infection process information is currently available here.

    3. Disease Information:

      No disease information is currently available here.

    4. Prevention:

      No prevention information is currently available here.

    5. Model System:

      No model system information is currently available here.

IV. Labwork Information

A. Biosafety Information:
  1. General biosafety information :
    • Biosafety Level: Biosafety Level 2 practices, containment equipment and facilities are recommended for all activities utilizing known or potentially infectious clinical materials or cultures. Animal Biosafety Level 2 facilities and practices are recommended for activities with experimentally or naturally infected animals (Website 42).
B. Culturing Information:
  1. Stool Culture :
    1. Description: For bacteriologic identification of Shigella, a bit of blood or mucus is seeded onto at least two different media. Generally, stool is plated lightly on a medium with only mild inhibiting factors for gram-negative growth, such as MacConkey's agar, xylose-lysine-deoxycholate agar, Tergitol-7, or eosin-methylene blue (EMB) agar, whereas a separate specimen is plated heavily on a more inhibitory medium such as Shigella-Salmonella medium. The more plates used, the greater the recovery yield. After overnight incubation at 37C, lactose negative colonies are transferred to triple-sugar agar and lysine-iron agar slants and reincubated. Those giving a characteristic reaction (alkaline slant, acid butt, and no gas) are tested biochemically and then serologically identified with Shigella grouping and typing antisera (Dupont, 2005). Specific diagnosis of shigella in stool specimens depends on the appropriate collection and transportation to the laboratory. Fresh stool samples collected from patients before initiation of therapy are preferred for microbiological tests because the chances of recovering the organisms are higher. For microbiologic cultures, fresh stool is preferred to rectal swabs in which the pathogens are less in number. Samples that cannot be cultured immediately should be kept in buffered glycerol-saline transport medium. Cary-Blair medium is the second option. Direct inoculation of culture plates at the bedside is the most efficient means of isolating shigella from the dysentery patients (Sur et al., 2004).

    2. Medium:
      1. Generally, stool is plated lightly on a medium with only mild inhibiting factors for gram-negative growth, such as MacConkey's agar, xylose-lysine-deoxycholate agar, Tergitol-7, or eosin-methylene blue (EMB) agar, whereas a separate specimen is plated heavily on a more inhibitory medium such as Shigella-Salmonella medium (Dupont, 2005). There is no reliably effective enrichment medium for all Shigella isolates, but gram-negative broth and Selenite broth are frequently used. For the optimal isolation of Shigella, two different selective media should be used; a general-purpose plating medium of low selectivity (e.g. MAC) and a more selective agar medium (e.g., xylose lysine desoxycholate agar [XLD]). Desoxycholate citrate agar (DCA) and Hektoen Enteric agar (HE) are suitable alternatives to XLD as media with moderate to high selectivities. Salmonella-shigella agar (SS) should be used with caution because it inhibits the growth of some strains of S. dysenteriae 1 (Bopp et al., 2003). Further identification can be made by using triple sugar iron (TSI) agar or Kligler iron agar (KIA), on which Shigellae are non-motile, produce an alkaline slant and acid butt due to inability to ferment lactose aerobically in the slope and the anaerobic fermentation of glucose in the butt, and fail to produce hydrogen sulphide or other gas (Sur et al., 2004).
    3. Optimal Temperature: 37C (Dupont, 2005)
  2. Culture and Serological tests to Identify Shigella Dysenteriae :
    1. Description: In brief, when this strain was subcultured onto Mac-Conkey agar (MA) and Salmonella-Shigella agar media, it produced non-lactose-fermenting colonies. Non-lactose-fermenting colonies were inoculated into Kligler iron agar, motility indole urea, and Simmons citrate agar media. The reactions in Kligler iron agar medium were acid butt and alkaline slant without production of gas and H2S. This strain was nonmotile and was negative for urea and indole in motility indole urea medium. It could not utilize citrate as a source of carbon. All of these biochemical reactions are typical of Shigella species. By slide agglutination, it was found that this strain agglutinated with S. dysenteriae type 1 antiserum, purchased from Wellcome Diagnostics (Dartford, England) (Islam et al., 1993).

    2. Medium:
      1. Mac-Conkey agar (MA) and Salmonella-Shigella agar media (Islam et al., 1993)
C. Diagnostic Tests :
  1. Organism Detection Tests:
    1. Fluorescent Antibody Staining of Shigella dysenteriae:
      1. Ontology: UMLS:xxx, GO:xxx, SNOMED:xxx, otherStd:xxx
      2. Time to Perform: 1-hour-to-1-day
      3. Description: An indirect fluorescent antibody test for rapid detection of Shigella dysenteriae 1 in diarrheal stools was developed. A diagnosis could be made within 90 min of submission of specimens to the laboratory. On comparison with culture results, the test had a sensitivity of 92%, a specificity of 93%, and positive and negative predictive values of 94% and 92%, respectively (Albert et al., 1992). Fluorescent bacteria were seen only in feces mixed with S. dysenteriae 1 and not other shigellae (Albert et al., 1992).
      4. False Negative: Five patients were positive by culture but negative by FAT (Albert et al., 1992) Some culture-positive specimens might have been missed by FAT because Shigella bacilli were not present in the portion of the stool taken for FAT (Albert et al., 1992).

  2. Immunoassay Tests:

    No immuno-assay tests available here.

  3. Nucleic Acid Detection Tests: :
    1. Shigella Detection by Culture and PCR:
      1. Time to Perform: 1-hour-to-1-day
      2. Description: In Bangladesh, the isolation rates of Shigella spp. range from 11% to 12% by the conventional culture technique. Since the sensitivity of this technique is low, the polymerase chain reaction (PCR) technique was used for detecting small number of Shigellae from patients' stools. Sensitivity and specificity of the two techniques were also compared. Stool samples were collected from 41 patients with dysentery who attended the Clinical Research and Service Centre of the ICDDR,B: Centre for Health and Population Research. All stool specimens were directly plated onto MacConkey, Salmonella-Shigella, Xylose lysin deoxycholate and Hectoen enteric agar media, and Shigellae were detected following standard procedures. DNA was extracted from the stool samples, and the target sequence of invasive plasmid antigen (ipa)H locus was amplified by PCR with 130 ng each of two primers (primer H8 [5'-GTTCCTTGACCGCCTTTCCGATAC-3'] and primer H15 [5'-GCCGGTCAGCCACCCTA-3']) following standard procedures. The amplified product was hybridized using an ipaH probe. The isolation rates of Shigella dysenteriae type 1, S. flexneri, S. sonnei, and S. boydii were, respectively, 17.1%, 19.5%, 4.9% and 2.4% by the conventional method. The results of the PCR technique showed that 700 bp fragment was generated in 18 of the 18 culture-positive and in 7 of the 23 culture-negative stools. One hundred twenty-three strains of Escherichia coli were also tested by PCR for identifying the enteroinvasive E. coli, but none of them yielded any positive result. This study showed that the sensitivity of the culture technique is 72% and specificity is 100%, when the PCR technique was considered as gold standard. Therefore, the PCR may be considered a more sensitive and specific technique than the conventional culture technique and has the potential to be employed in routine diagnosis of dysentery in clinical centres as well as in epidemiologic studies (Islam et al., 1998). The detection technique scheme, including the DNA extraction, DNA amplification and analysis of amplified products, requires only 5-6 hours compared to 18-24 hours of standard stool culture (Islam et al., 1998).
      3. Primers:
    2. PCR-ELISA_Detection of Shigella in Stools:
      1. Time to Perform: 1-hour-to-1-day
      2. Description: PCR techniques applied to diarrheal stools reliably diagnose Shigella and enteroinvasive Escherichia coli (EIEC) infections. Identification of PCR products using agarose gel electrophoresis (AGE) and hybridization with DNA probes has several shortcomings. Automated methods of identifying PCR products that process larger numbers of specimens can facilitate epidemiologic studies and standardize results. In this study, we used ELISA following PCR to detect ipaH gene sequences of Shigella and EIEC from 89 diarrheal stools. Results of ELISA were compared with AGE with and without DNA probe, and with culture. Two specimen preparation methods were compared as well: boiling/centrifugation, and purification with silicon dioxide (SiO2). Both PCR product-detection methods identified significantly more infections than did culture. PCR-ELISA detected significantly more infections than PCR-AGE when processed using SiO2 (P = 0.014). PCR-ELISA allows screening of larger numbers of specimens, automates test results, and avoids use of mutagenic reagents. PCR-ELISA is faster than PCR-AGE when testing large numbers of specimens, although not when testing small numbers of specimens (Sethabutr et al., 2000). PCR-ELISA requires about 6.5 hours, and is more convenient (Sethabutr et al., 2000). The potential benefit of PCR ELISA is less in the clinical diagnostic laboratory, where the costs of diagnosis may outweigh the benefits in comparison to empiric treatment. The benefit is greater in epidemiological studies, where a considerable proportion of currently undiagnosed infectious diarrhea cases can be explained by adding this technique to the diagnostic battery of tests, and the costs of diagnosis are relatively less important (Sethabutr et al., 2000).
      3. Primers:
    3. Multiplex PCR:
      1. Ontology: UMLS:xxx, GO:xxx, SNOMED:xxx, otherStd:xxx
      2. Time to Perform: unknown
      3. Description: We have developed two multiplex PCR assays that detect typical and atypical enteropathogenic Escherichia coli (EPEC) isolates, enteroaggregative E. coli (EAEC) isolates, enterotoxigenic E. coli (ETEC) isolates, enteroinvasive E. coli (EIEC) isolates, Shiga toxin-producing E. coli (STEC) isolates, and Shigella spp. The targets selected for each group were eae and bfpA for EPEC isolates, the target of probe CVD432 for EAEC isolates, the genes encoding heat-labile and heat-stable toxins for ETEC isolates, stx1 and stx2 for STEC isolates, and ipaH for EIEC isolates and Shigella spp. These PCRs were specific and sensitive for rapid detection of target isolates in stools. Among 150 stool specimens from the acute diarrhea tested, 9 samples (6%) had atypical EPEC, 9 (6%) had typical EPEC, 7 (4.7%) had EAEC, 3 (2%) had EIEC, 3 (2%) had Shigella spp., and 1 (0.7%) had an O26 STEC strain; we also detected mixed infections, 2 (1.3%) with EAEC and Shigella spp., 1 (0.7%) with atypical and typical EPEC strains, and another with atypical EPEC and EAEC strains. One of the multiplex PCRs directly applied to 36 stool specimens correctly identified 100% of EPEC and EAEC isolates (Aranda et al., 2004). In an epidemiological study, we compared standard methods, including colony blot hybridization, with multiplex PCR assays for the identification of diarrheagenic E. coli and Shigella spp. in the diarrhea of 150 children. There was total agreement between the results of multiplex PCRs and DNA hybridization for all tested isolates (Aranda et al., 2004).
    4. PCR-Detection of Shigella in Stools:
      1. Time to Perform: 1-hour-to-1-day
      2. Description: Analytical sensitivity (2 x 10(2) cfu) of the PCR technique was obtained by artificially spiking negative stool samples with a standard strain of S. flexneri type 2, then determining the detection limit. Specificity (100%) of the method was determined by testing a number of known Shigella and EIEC strains and organisms other than Shigella spp. A total of 300 stool samples collected from children with acute diarrhoea was plated onto two selective agar media after enrichment in Luria broth. Shigella spp. were isolated from 7.7% (23 of 300) and EIEC from 1% (3 of 300) patients. All enriched stool samples were subjected to PCR to amplify the target sequence of invasive plasmid antigen (ipa)H locus, a multicopy element found on the chromosome and invasion plasmid. The stool PCR was positive in 24 of the 26 culture-positive and in 22 culture-negative stools, thus detecting the presence of Shigella spp. or EIEC in 15.3% (46 of 300) of diarrhoea cases. When an ial probe was used for colony hybridistion with enriched stool cultures blotted on to membranes, 9.6% (29 of 300) of dysentery cases were identified as being caused by Shigella spp. or EIEC. Thus the sensitivity of enriched stool culture, colony hybridisation and enriched stool PCR was found to be 54%, 60% and 96%, respectively, when each of the methods was compared to the total microbiologically confirmed cases of dysentery. It was also observed that only 38% (48 of 126) of acute bloody dysentery cases actually had shigella or EIEC infection, as confirmed by laboratory methods. Moreover, this PCR assay could identify a number of untypable Shigella strains (Sh OUT), which would have remained undiagnosed had this assay not been used (Dutta et al., 2001). The ipaH PCR assay performed with enriched stool cultures is a highly sensitive and specific, rapid, simple and convenient test. It is useful if employed in epidemiological studies of dysentery (Dutta et al., 2001).
      3. Primers:

  4. Other Types of Diagnostic Tests:

    No other tests available here.

V. References

A. Journal References:
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C. Website References:
NCBI Taxonomy: Shigella boydii [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?lvl=0&id= 621 ].
NCBI Taxonomy: Shigella boydii BS512 [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?lvl=0&id= 344609 ].
NCBI Taxonomy: Shigella boydii Sb227 [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?lvl=0&id= 300268 ].
NCBI Taxonomy: Shigella dysenteriae [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?lvl=0&id= 622 ].
NCBI Taxonomy: Shigella dysenteriae 1012 [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?lvl=0&id= 358708 ].
NCBI Taxonomy: Shigella dysenteriae M131649 [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?lvl=0&id= 216598 ].
NCBI Taxonomy: Shigella dysenteriae Sd197 [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?lvl=0&id= 300267 ].
NCBI Taxonomy: Shigella flexneri [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?lvl=0&id= 623 ].
NCBI Taxonomy: Shigella flexneri 2a [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?lvl=0&id= 42897 ].
NCBI Taxonomy: Shigella sonnei [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?lvl=0&id= 624 ].
NCBI Taxonomy: Shigella sonnei 53G [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?lvl=0&id= 216599 ].
NCBI Taxonomy: Shigella sonnei Ss046 [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?lvl=0&id= 300269 ].
NCBI Entrez Genome Project: Shigella boydii BS512 project at TIGR [ http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=genomeprj&cmd=Retrieve&dopt=Overview&list_uids=15637 ].
NCBI Entrez Genome Project: Shigella boydii Sb227 project at Microbial Genome Center of ChMPH [ http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=genomeprj&cmd=Retrieve&dopt=Overview&list_uids=13146 ].
NCBI Entrez Genome Project: Shigella dysenteriae 1012 project at TIGR [ http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=genomeprj&cmd=Retrieve&dopt=Overview&list_uids=16194 ].
NCBI Entrez Genome Project: Shigella dysenteriae M131649 project at Sanger Institute [ http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=genomeprj&cmd=Retrieve&dopt=Overview&list_uids=346 ].
NCBI Entrez Genome Project: Shigella dysenteriae Sd197 project at Microbial Genome Center of ChMPH [ http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=genomeprj&cmd=Retrieve&dopt=Overview&list_uids=13145 ].
NCBI Entrez Genome Project: Shigella flexneri 2a str. 2457T project at Univ. Wisconsin [ http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=genomeprj&cmd=Retrieve&dopt=Overview&list_uids=408 ].
NCBI Entrez Genome Project: Shigella flexneri 2a str. 301 project at Microbial Genome Center of ChMPH [ http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=genomeprj&cmd=Retrieve&dopt=Overview&list_uids=310 ].
NCBI Entrez Genome Project: Shigella sonnei 53G project at Sanger Institute [ http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=genomeprj&cmd=Retrieve&dopt=Overview&list_uids=347 ].
NCBI Entrez Genome Project: Shigella sonnei Ss046 project at Microbial Genome Center of ChMPH [ http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=genomeprj&cmd=Retrieve&dopt=Overview&list_uids=13151 ].
NCBI Entrez Genome: Shigella boydii Sb227, complete genome [ http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=genome&cmd=Retrieve&dopt=Overview&list_uids=19008 ].
NCBI Entrez Genome: Shigella boydii Sb227 plasmid pSB4_227, complete sequence [ http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=genome&cmd=Retrieve&dopt=Overview&list_uids=19003 ].
NCBI Entrez Genome: Shigella dysenteriae Sd197 plasmid pSD1_197, complete sequence [ http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=genome&cmd=Retrieve&dopt=Overview&list_uids=19002 ].
NCBI Entrez Genome: Shigella dysenteriae Sd197, complete genome [ http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=genome&cmd=Retrieve&dopt=Overview&list_uids=19001 ].
NCBI Entrez Genome: Shigella sonnei Ss046 plasmid pSS, complete sequence [ http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=genome&cmd=Retrieve&dopt=Overview&list_uids=18731 ].
NCBI Entrez Genome: Shigella flexneri 2a str. 301, complete genome [ http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=genome&cmd=Retrieve&dopt=Overview&list_uids=257 ].
NCBI Entrez Genome: Shigella flexneri 2a str. 301 plasmid pCP301, complete sequence [ http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=genome&cmd=Retrieve&dopt=Overview&list_uids=17127 ].
NCBI Entrez Genome: Shigella flexneri 2a str. 2457T, complete genome [ http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=genome&cmd=Retrieve&dopt=Overview&list_uids=297 ].
NCBI Entrez Genome: Shigella dysenteriae 1012, unfinished sequence, whole genome shotgun sequencing project [ http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=genome&cmd=Retrieve&dopt=Overview&list_uids=5387 ].
NCBI Entrez Genome: Shigella sonnei Ss046, complete genome [ http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=genome&cmd=Retrieve&dopt=Overview&list_uids=18730 ].
NCBI Entrez Genome: Shigella boydii BS512, unfinished sequence, whole genome shotgun sequencing project [ http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=genome&cmd=Retrieve&dopt=Overview&list_uids=5333 ].
NCBI Entrez Genome: Shigella sonnei plasmid ColJs, complete sequence [ http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=genome&cmd=Retrieve&dopt=Overview&list_uids=15694 ].
NCBI Entrez Genome: Shigella flexneri virulence plasmid pWR501, complete sequence [ http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=genome&cmd=Retrieve&dopt=Overview&list_uids=15619 ].
NCBI Entrez Genome: Shigella flexneri 2a plasmid p2457TS2, complete sequence [ http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=genome&cmd=Retrieve&dopt=Overview&list_uids=15661 ].
NCBI Taxonomy: Shigella flexneri 5 [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?lvl=0&id= 373383 ].
NCBI Taxonomy: Gorilla gorilla gorilla [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?lvl=0&id= 9595 ].
NCBI Taxonomy: Pongo pygmaeus [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?lvl=0&id= 9600 ].
NCBI Taxonomy: Macaca sylvanus [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?lvl=0&id= 9546 ].
NCBI Taxonomy: Presbytis entellus [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?lvl=0&id= 9574 ].
NCBI Taxonomy: Presbytis cristata [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?lvl=0&id= 36232 ].
NCBI Taxonomy: Pan troglodytes [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=9598&lvl=3&lin=f&keep=1&srchmode=1&unlock ].
NCBI Taxonomy: Macaca silenus [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?lvl=0&id= 54601 ].
NCBI Taxonomy: Macaca nigra [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?lvl=0&id= 54600 ].
NCBI Taxonomy: Colobus guereza [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?lvl=0&id= 33548 ].
NCBI Taxonomy: Lophocebus albigena [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?lvl=0&id= 75567 ].
NCBI Taxonomy: Ateles geoffroyi robustus [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?lvl=0&id= 118645 ].
NCBI Taxonomy: Saimiri sciureus [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?lvl=0&id= 9521 ].
NCBI Taxonomy: Macaca mulatta [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?lvl=0&id= 9544 ].
NCBI Taxonomy: Aotus trivirgatus [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?lvl=0&id= 9505 ].
NCBI Taxonomy: Homo sapiens [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?lvl=0&id= 9606 ].
NCBI Taxonomy: Papio [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=9554&lvl=3&lin=f&keep=1&srchmode=1&unlock ].
NCBI Taxonomy: Canis familiaris [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?lvl=0&id= 9615 ].
NCBI Taxonomy: Felis catus [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?lvl=0&id=9685 ].
NCBI Taxonomy: Ateles belzebuth [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?lvl=0&id=9507 ].
NCBI Taxonomy: Alouatta pigra [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?lvl=0&id=182253 ].
NCBI Taxonomy: Ateles paniscus [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?lvl=0&id=9510 ].
NCBI Taxonomy: Cacajao rubicundus [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?lvl=0&id=70927 ].
NCBI Taxonomy: Cebus albifrons [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?lvl=0&id= 9514 ].
NCBI Taxonomy: Cebus apella [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?lvl=0&id= 9515 ].
NCBI Taxonomy: Cebus capucinus [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?lvl=0&id= 9516 ].
NCBI Taxonomy: Hylobates lar [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?lvl=0&id= 9580 ].
NCBI Taxonomy: Hylobates moloch [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?lvl=0&id= 81572 ].
NCBI Taxonomy: Lagothrix lagotricha [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?lvl=0&id= 9519 ].
NCBI Taxonomy: Macaca speciosa [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?lvl=0&id= 9553 ].
NCBI Taxonomy: Symphalangus syndactylus [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?lvl=0&id= 9590 ].
NCBI Genome Project: Shigella flexneri 5 str. 8401 project at Microbial Genome Center of ChMPH [ http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=genomeprj&cmd=retrieve&dopt=overview&list_uids=16375 ].
NCBI Taxonomy: Callithrix jacchus [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?lvl=0&id=9483 ].
NCBI Taxonomy: Saguinus nigricollis [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?lvl=0&id=9489 ].
NCBI Taxonomy: Shigella flexneri 2a str. 2457T [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?lvl=0&id=198215 ].
NCBI Taxonomy: Shigella flexneri 2a str. 301 [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?lvl=0&id=198214 ].
NCBI Taxonomy: Shigella flexneri 5 str. 84011 [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?lvl=0&id=373384 ].
Website 42: BMBL Section VII. Agent Summary Statements: BACTERIAL AGENTS [ http://www.cdc.gov/od/ohs/biosfty/bmbl4/bmbl4s7a.htm ].
Website 53: Shigella [ http://www.denniskunkel.com/advanced_search_result.php?keyword=shigella&osCsid=c3e4ce71796183f6e472ec41b8e874ed&x=0&y=0&search_in_description=1 ].
D. Thesis References:

No thesis or dissertation references used.

VI. Curation Information